MODULE 5│PHARMACEUTICS 1

DOSAGE FORM & DRUG DELIVERY SYSTEM

DOSAGE FORM & DRUG DELIVERY SYSTEMS USP Classification of Powders

I. INTRODUCTION TO DOSAGE FORMS Sieve number

• no. of square openings per linear inch
A. DEFINITION
Descriptive Term Sieve Number
Dosage Forms very coarse no. 8
• Drug products/preparations containing: coarse no. 20
• Active Pharmaceutical Ingredient (API)/ Drug moderately coarse no. 40
• Excipients/ Additives/Adjuncts fine no. 60
very fine no. 80
Drug Delivery System
• Drug products that allow the uniform release and targeting of Compounding of Powders
drugs into body
1. Comminution
Drug
• an agent intended for use in diagnosis, cure, treatment, a. Trituration
mitigation or prophylaxis in man and other animals – affects • mortar and pestle
the structure or any function of the body
b. Levigation
Excipients (aka adjuncts or additives) • forming a paste by the addition of a levigating agent (ex.
• nontherapeutic ingredients which improve the physical mineral oil, glycerin)
characteristics and efficacy of a drug in a dosage form
• Role: drugs → more appealing and efficacious c. Pulverization by Intervention
• Use: solubilize, suspend, emulsify, dilute, stabilize, • addition of volatile substance to a gummy material (ex.
preservatives, color, flavor, etc. camphor + alcohol; I2crystals + ether)

Cosmetics 2. Mixing/ Blending

• any substance/preparation intended to be placed in contact
with external parts of human body or with teeth and mucous a. Trituration
membranes of oral cavity • mortar and pestle
• with a view exclusively or mainly to cleaning them, perfuming
them, correcting body odors, changing their appearance, Types of mortar and pestle
protecting them and/or keeping them in good condition • Glass – smooth non-porous surface; for simple admixture;
for chemicals that stain
Food Supplement • Porcelain – rough inner surface; for comminution
• processed food products that help supplement the diet • Wedgewood – rougher surface; for crystalline substances
• may contain dietary ingredients such as vitamins, minerals,
herbs, amino acids, and other dietary substances b. Spatulation
• make take various forms including those of liquids, capsules, • Blending of powders with a spatula on a tile or paper
powders, etc., except parenteral • Use: small quantities, non-potent drugs, eutectic mixtures

Compounding c. Sifting
• process of combining, mixing, or altering ingredients to • Powders are passed through sifters
create a medication tailored to the needs of an individual • Results in light, fluffy product
patient. • Not for potent substances

B. LOCAL & SYSTEMIC EFFECTS d. Geometric Dilution

• addition of an equal volume of diluent to a potent substance
Local effects placed in a mortar
• felt in general area of administration Step 1: 100mg of potent drug + 100mg of diluent = 200mg of mixture
• common route: topical Step 2: 200mg of mixture + 200mg of diluent = 400mg of mixture
Step 3: 400mg of mixture + 400mg of diluent = 800mg of mixture
Systemic effects Step 4: 800mg of mixture + remaining diluent = 1000mg of mixture
• occur in tissues distant from the site of contact between the
body and the drug e. Tumbling
• drug must enter the bloodstream • large containers rotated by a motorized process
• common route: oral and parenteral
Types of Powders
II. SOLID DOSAGE FORMS
1. Bulk Powders – dispensed in large quantities
A. POWDERS
a. Oral Powders
• mixtures of finely divided drugs and/ or chemicals in a dry • dissolved in water prior to use
form which may be intended for internal or external use
• Advantages: b. Dentifrices
• rapid dispersion of ingredients • used to clean and polish teeth
• flexibility in compounding • contain a soap, mild abrasive and anticariogenic agent
• good chemical stability
• Disadvantages: c. Dusting Powders
• inaccuracy of dose • locally applied non-toxic powders that have no systemic
• not suitable for unpleasant-tasting, deliquescent and action
hygroscopic drugs
d. Douche Powders
• dissolve in warm water prior to introduction into a body cavity

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e. Insufflations a. Compressed Tablets
• blown into body cavities using an insufflator • formed by compression
• some are scored
f. Trituration
• dilutions of potent powdered drugs (10% API) b. Multiple Compressed Tablets
• Layered tablets – formed by compressing 2 or 3 layers of
2. Divided Powders/Chartulae – dispensed in individual doses formulation against each other (ex. Neozep tablet)
usually in folded papers; block-and-divide method • Compression coated tablets – formed by compressing an
outer shell around a tablet core
Types of Powder Paper
c. Coated Tablets
a. White Bond Paper • Sugar Coated Tablets – coated with sucrose-based solution
• opaque paper with no moisture resistance • Film Coated Tablets – coated with a thin layer of polymer
material
b. Vegetable Parchment • Enteric-Coated Tablets – remain intact in the stomach but
• thin, semi-opaque, moisture resistant paper disintegrate in the small intestine

c. Glassine Paper 2. Tablets Used in the Oral Cavity

• glazed transparent moisture-resistant paper
a. Chewable Tablets
d. Waxed Paper • chewed first before swallowing
• transparent waterproof paper; suitable for deliquescent and • diluent: mannitol and xylitol
hygroscopic drugs • (ex. Multivitamins, antacids)

B. GRANULES b. Rapidly/ Orally Disintegrating Tablets

• liquefy on the tongue and then the patients swallow the liquid
• dry aggregates of powder particles • (ex. Risperidone, Ondansetron)
• Normal sieve no. 4 to 12
• Tablet formulation: sieve no. 12 to 20 c. Buccal Tablets
• placed in the lining of the cheeks
Advantages of Granules over Powder • disintegrate slowly (4 hours)
• (ex. Progesterone)
• Flow well compared to powders
d. Sublingual Tablets
• Less tendency to cake or harden
• More stable to humidity • placed under the tongue for systemic absorption
• More easily wetted by liquids • disintegrate rapidly (2-3 minutes)
• (ex. Nitroglycerin, ISDN)
Compounding of Granules
e. Lozenges
• solid dosage forms in a hard candy or sugar base that
1. Wet Granulation dissolve slowly in mouth for local effect
• addition of granulating fluid or liquid binder • (ex. Strepsils® - dicholorobenzyl alcohol + amylmetacresol)
• most common; • Types:
• Troches – compressed lozenges
2. Dry Granulation • Pastilles – molded lozenges
• for moisture-sensitive and heat labile materials • Lollipops – lozenges on sticks
• use compaction/ compression forces
3. Tablets Used to Prepare Solutions
3. Effervescent Granules
• dissolved in water before use in which CO2 gas is released a. Effervescent Tablets
to mask the unpleasant taste of drug • Release CO2 upon dissolution in water
• Components: • ex. Berocca®, Alka-Seltzer® - antacid + pain reliever
• Sodium bicarbonate
• Citric acid →sticky b. Compounding/ Dispensing Tablets
• Tartaric acid →crumble • contain a large amount of API used by pharmacists in
• Preparation: compounding multiple dosage units
• Dry/Fusion Method – binder is 1 molecule of water in • no longer use
citric acid
• Wet Method – binder is water + alcohol c. Hypodermic Tablets
• used by physicians to prepare parenteral solutions
C. TABLETS • no longer use
• solid dosage forms which are prepared mainly by d. Molded Tablets/ Tablet Triturates
compression or molding • prepared by moistening powders and then putting on a
• Advantages: triturate mold (may be compressed)
• uniform content • results to cylindrical tablets which are very soluble in water
• less manufacturing cost
• easy to package and ship D. CAPSULES
• simple to identify
• most stable of all oral dosage form • solid dosage forms in which the drug is enclosed within in
• tamperproof either a hard or soft, soluble shell, usually made of gelatin
• Disadvantages: • Gelatin – partial hydrolysis of collagen from the skin/bones
• some drugs resist compression of animals
• some drugs that require encapsulation prior to • Types:
compression • Type A – mainly from pork skin; acid processing
• Type B – from bones and animal skins; alkaline
Types of Tablets processing
• Vegetable Capsules – alternative hydroxypropyl
1. Tablets for Oral Ingestion methylcellulose (HPMC) or hard starch

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Types of Capsules:

1. Hard Gelatin Capsules

Plasma concentration

Plasma concentration
• dry-filled or two-piece capsules (cap and body) Immediate
• main components: gelatin, sugar and water Sustained
• additives: colorant, opacifying agent (TiO2) + SO2 [0.15%] (to
prevent decomposition of gel)
• moisture content: 12-16%
• stored at 21-25°C/30-35% RH Time Time
• capsule sizes: (increase capsule size = decrease capacity)
• Human – No. 5 (smallest) – No. 000 (largest) Controlled Release
• Veterinary – No 10. – No. 12 Sustained Release
• Other designs:
• Pulvule – tapered at one end 2. Delayed-Release
• Spansule – tapered at both ends • drug release is other than the time of prompt administration
• Ex: enteric-coated
2. Soft Gelatin Capsules
• one-piece capsules 3. Repeat Actions
• used to contains non-aqueous liquids (vitamin e, cod liver oil, • contains 2 single doses of a medication
digoxin), suspensions, pastes, and dry materials • (1st dose → immediate; 2nd dose → delayed)
• main components: gelatin, plasticizer (glycerin, sorbitol) and
preservatives against fungi 4. Targeted Release
• moisture content: 6-10% • drug release is isolated in a specific body region/ tissue →
• no specific sizes absorption and action

E. ORAL MODIFIED-RELEASE SOLID DOSAGE FORMS • Colonic Tablets – deliver the drug into the colon without
dilution in other regions of GIT
• drug release features are based on time, course and • Gastro Retentive Tablets – remain in the stomach for long
locations period (floating tablets)
• Advantages:
• Economic savings F. PHARMACEUTICAL INSERTS
• Avoid patient compliance problems
• Reduce fluctuation in drug level (to prolong therapeutic 1. Suppositories
effect → to reduce dosing frequency) • Solid or semisolid masses intended to be inserted into a
• Minimize or eliminate side effects body orifice for local or systemic effect; they will melt at body
temperature or dissolve into aqueous secretions of body
Mechanism of Immediate-Release Formulation cavity
• Used when oral route is inadvisable
• Disadvantages
MTC • Inconvenient
Plasma concentration

• Erratic absorption

Types of suppositories

Rectal Vaginal (Pessaries) Urethral (Bougies)

bullet, torpedo, little globular, ovoid, cone pencil-like
MEC finger
2 g (adult) 5g 4 g (male)
Duration 1 g (children) 2 g (female)
32 mm (adult) varies 140 mm (male)
onset Time 16 mm (children) 70 mm (female)

a. Rectal
Plasma concentration

• Advantages
• Low cost and lack of technical difficulties compared to
cmax
parenteral therapy
• Partially avoid the first-pass-effect
• Ex. Bisacodyl
• Disadvantages
• Surface area for absorption is smaller
AUC • Defecation may interrupt absorption
• Fluid content is less
• More expensive compared to oral dosage forms
Time • Stigma of violating patient’s dignity
tmax
b. Vaginal
• Indicated for bacterial or fungal infections and HRT
Types of Modified-Release Dosage Forms
• May be in the form of tablet, suppository, and semisolids
• Buffered to pH of 4.5
1. Extended-Release
• provides a prompt desired effect followed by a gradual c. Urethral
release of remaining amount • Inserted into the urethra after urination
• Problem: dose dumping • Ex: Alprostadil micro suppository
• Types:
• Controlled Release – zero order Suppository Bases
• Sustained Release – first order • Criteria:
• Inert, non-irritating, and non-sensitizing
• Firm and does not melt at RT
• Dissolves rapidly in the cavity fluid

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a. Oleaginous Base • Example:
• Cocoa Butter – most common and good base for rectal • Polyethylene Glycol (PEG) Ointment
suppository; solid at 32°C, melts at 34-35°C; exhibits • MW < 600 → clear, colorless liquids
polymorphism (ȣ - least stable [18°C]; α; β’; β – most stable • MW 600-1000 → semisolids
[34.5°C] • MW > 1000 → white, wax-like solids
• Wecobee – from coconut oil
• Witepsol – lauric acid is the major component; saturated B. CREAMS
fatty acids (C12-C18)
• semi-solid preparations containing 1 or more APIs dissolved
b. Water-Soluble/Miscible Base or dispersed in either w/o or o/w emulsion
• Glycerinated Gelatin – most common base for vaginal • soft, spreadable consistency
suppositories • Examples:
• Polyethylene Glycol (PEG) • Vanishing Creams – o/w base; large % water (ex.
glycerin, propylene glycol – + stearic acid)
1. Vaginal Tablets/Inserts • Cold Creams/ Petrolatum Rose Water Ointment –
• Ovoid or bullet-shaped tablets inserted into the vagina using w/o base; mineral oil → less rancid; white wax;
a plastic inserter for local effects spermaceti (cetyl esters wax) + Na borate
• contains antimicrobial agents • Components
• Aqueous solution
2. Implants/Pellets • Oleaginous portion
• long-acting dosage forms that provide continuous release of • Emulsifying agent
the drug to the body • Humectant
• administered parenterally or subcutaneously • Preservatives
• Pellet implants – small, sterile, cylindrical masses
• Levonorgestrel (Norplant ®) – 5 years C. GELS
• Leuprolide acetate (Viadur®) – prostate cancer 1 year
• clear, transparent, and non-greasy semisolids, containing
III. SEMISOLID DOSAGE FORMS API(s) dissolved in aqueous liquid, rendered jelly-like by the
addition of gelling agent
A. OINTMENTS

• semisolid dosage forms intended for external use Phenomena in Gels

• Uses:
• emollient 1. Thixotropy – reversible gel-sol formation
• occlusive 2. Imbibition – taking up of liquid without an increase in size
• vehicle 3. Swelling – taking up of liquid with increase in size
4. Syneresis – liquid is squeezed out and the gel shrinks, forming a
Ointment Bases: Xerogel

1. Oleaginous/ Hydrocarbon Base D. PASTES

• have emollient, occlusive
• greasy, anhydrous, non-water washable • semisolid preparations containing a large proportion of solid
• Examples: material (≥25%) and therefore stiffer than ointments
• Petrolatum, USP (Yellow Petrolatum, Petroleum • Use: to prolong contact of drug
Jelly or Vaseline®) – purified mixture of semisolid • Zinc Oxide Paste (ZnO) – treatment of diaper rash
hydrocarbon from petroleum
• White Petrolatum, USP – bleached or decolorized E. PLASTERS
• Yellow Wax (Beeswax) – wax obtained from the
honeycomb of Apis mellifera • solid or semisolid adhesive masses spread on a backing
• White Wax – bleached or decolorized material (paper, fabric, moleskin or plastic)
• Yellow Ointment, USP (Simple Ointment) – yellow • Use:
petrolatum + yellow wax • Protection and mechanical support
• White Ointment, USP – white petrolatum + white wax • Provide prolonged and close contact with the skin
• Salicylic Acid Plaster – keratolytic (10-40% salicylic acid)
2. Absorption Base
• without emulsion F. POULTICES/ CATAPLASM
• greasy and non-water-washable
• less emollient and occlusive effects • soft, moist masses of meal, herbs, seeds, etc.; applied hot in
• can absorb small amounts of water a cloth that consists of gruel-like consistency
• Examples: • Use: to localize infectious materials and counterirritant
• Hydrophilic Petrolatum, (Aquaphor) – white • Kaolin Poultice – treatment for boils and anti-inflammatory
petrolatum + white wax + cholesterol + stearyl alcohol
• Lanolin, USP (Anhydrous lanolin) – wax-like G. PLEDGETS
substance from the wool of sheep Ovis aries containing
0.25% moisture • Small compress or tuft, usually of cotton or cotton wool, used
• Hydrous Lanolin – 25% moisture to apply disinfectant or medicament to the skin
• Modified Lanolin – without free lanolin alcohols
and excess detergents H. GLYCEROGELATIN

3. Water-Removable Base • plastic masses applied on skin with a fine brush

• o/w emulsions or creams • components:
• easily washed off with water • 40% glycerin
• may be diluted with large amounts of water • 35% water
• Example: • 15% gelatin
• Hydrophilic Ointment • 10% API
• Zinc Gelatin Boot – treatment of varicose ulcers
4. Water-Soluble Base
• lipid-free
• greaseless and water-washable
• used for incorporation of solid materials

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 IV. TRANSDERMAL DRUG DELIVERY SYSTEMS V. LIQUID DOSAGE FORMS

• controlled release DDS or patches that allow the passage of A. SINGLE PHASE SYSTEMS
drugs from the skin to the systemic circulation
• Advantages: SOLUTIONS
• Constant dosage can be maintained
• Avoids first pass effect • liquid preparations containing one or more substances
• Reduced need for active administration dissolved in a suitable solvent
• Noninvasive compared to parenteral therapy • Advantages
• Can be promptly interrupted by removal • homogenous dose
• Disadvantages: • immediate availability for absorption
• Skin structure poses a barrier on the MW of the drug • flexibility
• Usually reserved for extremely potent drugs • Disadvantages
• Drug should have adequate solubility in both lipophilic • bulky
and aqueous environments • difficult to mask unpleasant taste and odor
• Development of contact dermatitis • less stable than solid dosage forms → degrade more
rapidly
Types of TDDS • interact with another component
• leaching: container → solution
1. Monolithic Systems • sorption: solution → container
• Incorporate matrix layer (polymer with dispersed drug)
beneath the backing layer Solubility

2. Membrane-controlled Systems Descriptive Term Parts of Solvent Required for 1

• Contain a drug reservoir or pouch (liquid or gel) and a rate- Part of Solute
controlling membrane Very Soluble <1
Freely Soluble 1-10
Parts of TDDS Soluble 10-30
Sparingly Soluble 30-100
Slightly Soluble 100-1,000
1. Occlusive Backing Layer Very Slightly Soluble 1,000-10,000
• protects the patch from outer environment Insoluble >10,000
• prevents drug loss and water loss
Pharmaceutical Solvents/ Diluting Agents
2. Drug Reservoir/ Matrix System
• stores and releases the drug at the skin site
1. Water
• most common
3. Rate controlling membrane
Official Types of Water
• controls drug release from the reservoir in membrane-
controlled systems
a. Purified Water
4.. Adhesive Layer • obtained by distillation, ion exchange, reverse osmosis
• ensures contact of the patch to the skin • used for aqueous dosage forms except parenteral and other
sterile solutions
5.. Release Liner b. Water for Injection
• protects the drug during storage and is removed prior to use c. Sterile Water for Injection
d. Bacteriostatic Water for Injection
Examples e. Sterile Water for Inhalation
Drug Use Application f. Sterile Water for Irrigation
Scopolamine Motion sickness (1st Behind the ear every
(Transderm Scop®) TDDS developed) 3 days 2. Alcohol
Nitogylcerin (Deponit®) Prophylactic Upper part of body • aka ethyl alcohol/ ethanol/ C2H5OH
treatment of angina once daily • can dissolve water-insoluble substances
Clonidine 1st TDDS for HTN Upper part of body • used with co-solvents such as glycols and glycerin
(Catapres-TTS®) every 7 days
Nicotine Smoking cessation Upper part of body Alcohol Content Limit
(Nicoderm®) once daily
• proposed by FDA to manufacturers of OTC oral products
Fentanyl Breakthrough pain Upper part of body
Age Limit
(Duragesic®) every 3 days
Methylphenidate ADHD Hip area 2 hours <6 years old 0.5%
(Daytrana®) before an effect is 6 to 12 years old 5%
needed > 12 years old 10%
Estradiol HRT Lower abdomen or
(Climar®) upper buttocks twice Types of Alcohol:
daily
Testosterone HRT Androderm® - upper
a. Alcohol, USP
(Androderm®, part of body or thighs
Testoderm®) Testoderm® - scrotum • 94.9% to 96.0% v/v ethanol

Application b. Dehydrated alcohol

• NLT 99.5% v/v ethanol
• site of application should be rotated c. Rubbing alcohol
• cur or dry-shave first the hair before pacing the patch • 70% v/v ethanol, the remainder consisting of water and
• it may be left on when showering, bathing or swimming denaturant
• use of skin lotion should be avoided at the application site • Denaturant: 8 parts acetone, 1.5 parts methyl isobutyl
ketone, 100 parts ethyl alcohol

d. Isopropyl Rubbing Alcohol

• 70% v/v isopropyl alcohol, the remainder consisting of water

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3. Glycerin • Evacuation Enema – to evacuate the bowel (ex. Fleet
• clear, syrupy liquid with a sweet taste Enema) – sodium phosphates enema
• miscible with both water and alcohol • Retention Enema – retained in the intestine for systemic
• has humectant, emollient and preservative qualities absorption (ex. Sulfasalazine Enema) – ulcerative colitis

4. Propylene Glycol f. Mouthwashes

• viscous liquid • aqueous solutions used by swishing the liquid in the oral
• miscible with both water and alcohol cavity to cleanse the mouth
• can be used as substitute for glycerin • May contain alcohol
• Use: therapeutic, cosmetic
5. Fixed Oils
• usually of vegetable origin g. Gargles
• can also use mineral oil for stability • aqueous solutions used for treating pharynx and
• Examples: nasopharynx by forcing air from the lungs through the
• Corn oil solution held in the throat
• Cottonseed oil
• Peanut oil 2. Sweet and Other Viscid Aqueous Solutions
• Sesame oil • Viscous liquids or semisolids
• Contain sugars, polyols, and/ or polysaccharides
Classifications of Solution
a. Syrups
1. Aqueous Solution • Concentrated aqueous solutions of sugar or sugar substitute
• Solvent or vehicle is mainly water with or without flavoring agents and medicinal substances
• May contain alcohol as preservatives
a. Aromatic Water/Medicated Waters
• clear, saturated aqueous solutions of volatile oils or other Types of Syrups
aromatic substances
• Use: flavored /perfumed vehicles for water soluble drugs i. Simple Syrup/ Syrup NF
• Examples: • 85% w/v or 65% w/w
• Peppermint Water, USP • sp. gr. = 1.313
• Stronger Rose Water, USP • self-preserving at ≥65% sugar
• Preparations: • low solvent capacity for drugs
• Distillation – universal but not practical/ economical
• Used for Preparing Stronger Rose Water, Orange ii. Flavored Syrups
Flower Water • syrups containing flavoring agents but not medicinal
• Simple Solution – more economical and simpler substances
• Talc may be used as dispersant • Examples:
• Instability: Salting out – formation of insoluble layer at top • Orange and Cherry syrup – acidic medium
• Cocoa syrup – bitter
b. Diluted Acids • Raspberry syrup – sour and salty
• prepared by diluting concentrated acids with purified water • Glycyrrhiza – masks bitterness of the complex vitamins
• expressed on a %w/v basis • Acacia syrup – masking bitter taste for urea
• most have strength of 10% w/v with the exception of diluted • Eriodictyon syrup – masking bitter taste for alkaloids
acetic acid
• Example: iii. Medicated Syrups
• Diluted HCl – treatment for achlorhydria; taken with • Simple or flavored syrups with API(s)
straw • Examples:
• Dextromethorphan + Guaifenesin
c. Topical Solutions • Diphenhydramine
• Astringent – locally applied solutions that precipitate • Ipecac
proteins and cause constriction of the skin
• Aluminum Acetate (Burrow Solution) – 5% aqueous Preparations of Syrups
solution; wet dressing in contact dermatitis
• Calcium Hydroxide (Limewater or Liquor calcis) – Solution with Heat
0.14% aqueous solution; more soluble in cold water • fastest methods
• Coal Tar (LCD) – 20% alcoholic solution; for eczema • problem: overheating may cause sucrose inversion/
• Anti-infective agents caramelization
• Hydrogen peroxide (Agua oxinada) – 3% aqueous or
10 volumes solution; anti-infective Solution without Heat
• Povidone Iodine (Betadine) – 10% aqueous solution; • avoids sucrose inversion
anti-infective
• Chlorhexidine gluconate – 4% aqueous solution; Percolation
0.12% solution is used as antiplaque mouthwash • preferred
• Thimerosal (Merthiolate) – 0.1% solution • water is passed through a bed of sucrose in a column
• slow rate (1mL/min) → to prevent bubbles (oxidation)
d. Douches
• aqueous solutions directed against a part into a cavity of the Reconstitution
body • addition of sugar to a medicated liquid
• Use: cleansing or antiseptic agent • addition of medicated liquid to syrup
• Examples:
• Eye Douche – removes foreign particles and b. Linctuses
discharges • viscous oral liquid that contains one or more active
• Pharyngeal Douche – throat ingredients dissolved in a suitable base that generally
• Vaginal Douche – maintain the acidic pH of the vagina contains a higher concentration of sugar or other sugars
(ex. pH Care® - chlorhexidine gluconate) • indicated for cough and colds

e. Enemas c. Honeys
• aqueous solutions administered rectally for either local or • thick liquid preparations somewhat allied to syrups but using
systemic effect honey as a base
• Types:

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d. Mucilage a. Liniments (Embrocation)
• thick, viscid, adhesive liquids • alcoholic or oleaginous solutions of various APIs intended to
• Preparation: be rubbed on the skin
• Dispersion of gum in water • Types:
• Extraction of mucilaginous principles with water • Alcoholic – counterirritant, rubefacient and penetrating
• Examples: action
• Acacia Mucilage • Oleaginous – massage; less irritating
• Tragacanth Mucilage b. Collodions
• Liquid preparations composed of pyroxylin dissolved in a
e. Jellies solvent mixture usually composed of 3:1 mixture of ether and
• Class of gels in which the structural coherent matrix contains alcohol
a high portion of water
Pyroxylin
• Uses:
• cotton + HNO3 + H2SO4 (act as catalyst)
• Lubricant (ex: K-Y Jelly)
• aka nitrocellulose, collodion cotton, soluble guncotton
• Contraceptive (ex: Nonoxynol-9)
• harsh to touch and flammable
• Topical anesthetic (ex: Lidocaine)
• Uses:
3. Alcoholic or Hydroalcoholic Solutions • Occlusive protective coating to the skin
• Solvent may be either pure alcohol or alcohol mixed with • Applied using a hair brush
water • Water repellant
• Types:
a. Elixirs • Flexible Collodion
• Clear, sweetened or flavored, hydroalcoholic solutions • +3% castor oil – flexible
intended for oral use • +2% camphor – waterproof
• Alcohol content: 5-40% • Salicylic Acid Collodion
• may contain glycerin and syrup • 10% salicylic acid in flexible collodion
• self-preserving at >10% alcohol • Keratolytic
• Elixirs vs. Syrups
• Less sweet c. Oleo vitamins
• Less viscous • Fish liver oils diluted with edible vegetable oil or solutions of
• More stable and more easily prepared vitamins in fish liver oil
• Less effective in masking unpleasant taste
• Preparations: d. Extracts
• Simple Solution • medicinally active portions of vegetable drugs which have
• Admixture of 2 Medicated Liquids been isolated using a solvent or solvent mixture
• Types:
• Medicated Elixir – digoxin, phenobarbital, Methods of Extraction:
diphenhydramine, dexamethasone
• Non-Medicate Elixir – aromatic elixirs, iso-alcoholic • Maceration – soaking
elixir – better solvent; higher content • Digestion – maceration with gentle heat
• Infusion – maceration in hot or cold water
b. Tinctures • Decoction – boiling in water
• alcoholic or hydroalcoholic solutions prepared from • Percolation – passage of solvent through column of the
vegetable drugs or chemical substances drug
• Alcohol content varies Forms of Extracts:
• Strength: 10% w/v
• Preparations:
• Semi-Liquid Extract – syrupy consistency prepared without
• Process P – percolation (ex. Belladonna Tincture)
the intent of removal the menstruum
• Process M – maceration (ex. Sweet Orange Peel
• Pilular/ Solid Extract – plastic consistency prepared with
Tincture)
nearly all of the menstruum
• Simple Solution – Iodine Tincture (2% in 50% alcohol);
• Powdered Extract – prepared to be dry by the removal of all
• Examples:
menstruum
• Laudanum – Opium Tincture
• Paregoric – Camphorated Opium Tincture
B. DISPERSE SYSTEMS
• Green Soap Tincture – topical detergent
• Iodine Tincture – topical anti-infective
• contain undissolved or immiscible drug distributed
• Compound Benzoin Tincture – topical protectant
throughout a liquid vehicle
• Phases:
c. Spirits/ Essences
• Dispersed Phase
• hydroalcoholic solutions of volatile oils
• Dispersed Medium
• Alcohol content: 50-90%
• Types:
• Preparations:
• Colloidal Dispersion: 1 nm – 0.5 μm
• Simple Solution – (ex: aromatic ammonia spirit)
• Fine Dispersion: 0.5 – 10 μm
• Solution with Maceration – (ex: peppermint spirit)
• Coarse Dispersion: 10 – 50 μm
• Chemical Reaction – (ex: ethyl nitrite spirit)
• Distillation – (ex: brandy spiritus vinivitis; whisky
Disperse Systems
spiritus frumenti)
1. Suspensions
d. Fluidextracts
• liquid preparations containing insoluble, solid drug particles
• hydroalcoholic solutions from vegetable drugs (ONLY)
(suspensoid) dispersed throughout a liquid vehicle
prepared by percolation
(suspending medium)
• “100% Tinctures” - too potent and too bitter
• Reasons
• Preparation:
• Improved stability
• Percolation
• Enhanced palatability
• Example:
• For drugs insoluble in a specific liquid
• Cascara Sagrada Fluidextract – cathartic
• Desired Features:
• Fine, uniform-sized particles
4. Other Non-Aqueous Solutions
• Slow rate of sedimentation
• Solvent may be ethereal or oleaginous
• Ease of redispersion
• Pour readily and evenly from its container
Module 5 – Dosage form & Drug Delivery System Page 7 of 9 RJAV 2022
Types of Suspensions

a. Gels
• Examples:
• Betamethasone Gel – anti-inflammatory
• Tretinoin Gel – keratolytic
• Aluminum Hydroxide Gel – antacid
• Phenomena in Gels c. Interfacial Film Theory (Plastic Theory)
• Imbibition – no increase in size • the emulsifier forms an interface between the oil and water,
• Swelling – increase in size surrounding the droplets of the internal phase as a thin layer
• Syneresis – gel shrinks of film adsorbed on the surface of the drops
• Xerogel – formed when only framework remains
d. Viscosity Theory
b. Magmas/ Milks • the viscosity of the medium aids in the emulsification by the
• Aqueous suspensions of large, insoluble inorganic drugs mechanical hindrance to coalesce the globules
giving them a whitish color compared to gels
• Examples: Methods of Emulsion Preparation
• Bentonite Magma – suspending agent
• Milk of Magnesia [Mg(OH)2] – antacid Dry Gum (Continental) Method
• 4(oil): 2(water): 1(gum)
c. Lotions • oil + gum, then add water all at once
• liquid suspensions or dispersions intended for external • w/o
application to the body
• Examples: Wet Gum (English) Method
• Calamine Lotion – ZnO + ferric oxide; trituration; • 4(water): 2(oil): 1(gum)
antipruritic; • water + gum, then add oil gradually in small portions
• White Lotion – ZnSO4 + sulfurated potash; • o/w
astringent, protective and mild antibacterial action
Forbes Bottle Method
d. Mixtures • for volatile oils or fixed oils of low viscosities
• Contain API which are dissolved or suspended in a liquid • the gum and oil are shaken in a bottle; then water is added in
vehicle portions
• Examples: • 3:2:1 or 2:2:1
• Bordeaux Mixture (CuSO4 + CaO) – algaecide in pools
• Kaopectate (Kaolin + Pectin) – antidiarrheal Nascent Soap/ In Situ Soap Method
• formation of a soap by mixing equal volumes of oil and an
2. Emulsions aqueous alkali solution
• Prepared by combining 2 immiscible liquids, one of which is • soap formed acts as an emulsifier
dispersed throughout the other
• Components VI. STERILE DOSAGE FORMS
• Internal Phase – discontinuous/ dispersed phase
• External Phase – continuous phase/ dispersion • dosage forms that are required to have absence of living
medium microorganisms including its spores
• Emulsifying agent – reduces interfacial tension • Examples:
• Parenteral – injectable
• Ophthalmic – eyes
Types of Emulsions • Inhalations
• Irrigation solution
a. Oil-in-water (o/w) • Dialysis Solutions
• oil id the dispersed phase & water is the dispersion medium • Implants
b. Water-in-oil (w/o)
• water is the dispersed phase and oil is the dispersion A. PARENTERALS
medium
• Injected through the skin or directly into the body
c. Multiple Emulsions • Must conform to strict requirements for microbiological
• the dispersed phase contains smaller droplets that have the impurity, particulate matter, pyrogenicity and isotonicity
same composition as the external phase
• w/o/w or o/w/o Parenteral Routes

d. Microemulsions 1. Intravenous (IV)

• clear, stable, liquid mixtures of oil, water, and solubilizer • Directly into the systemic circulation (back of the hand or
• vs. Macro emulsions: dorsal forearm
• clear, transparent liquid • Can be injected at all one (IV bolus) or gradually over a
• 10-200 nm diameter sustained period of time (IV infusions)
• formed by simple mixing 2. Intramuscular (IM)
• thermodynamically stable • Deep into the skeletal muscles (gluteal or deltoid muscle)
• For greater volume (2 to 5 mL)
Theories of Emulsification • Ex: vaccines, antipsychotics
3. Subcutaneous (SC/ SQ)
a. Surface Tension Theory • Injected into loose connective and adipose tissue (lower
• the internal forces in liquid droplet promote association of the abdomen, upper arm, anterior thigh)
molecule of the substance resisting distortion of the droplet • Small volumes (1.3 mL or less)
into a less spherical form • Ex: Insulin
4. Intradermal (ID)
b. Oriented Wedge Theory • Into the corium of the skin
• the surfactant forms monomolecular layers around the • Minimal volume (0.1 mL)
droplets of the internal phase of the emulsion • Ex: tuberculin skin tests
5. Intracardiac
• Heart chamber

Module 5 – Dosage form & Drug Delivery System Page 8 of 9 RJAV 2022
6. Intra-arterial C. INHALATIONS
• Artery
7. Intraspinal • Administered directly into the lungs for local action on the
• Vertebral column bronchial tree or systemic action
8. Intrathecal • may be in form of dry powders or solutions
• Cerebrospinal fluid • Advantages:
9. Intra-articular • Large area for absorption
• Joint space • Good blood supply
10. Intrasynovial • Avoids first pass effect
• Joint fluid • Example: Budesonide (Budecort®)
11. Epidural
• Near the dura mater of the CNS D. IRRIGATION

Components of Parenteral • Used to wash, soak, or flush wounds, surgical openings, or

body tissues
1. Solvent/ Vehicle – carrying agent • Usually packaged in large volume containers
• Examples:
a. Aqueous • Sodium Chloride Irrigation
• Water for Injection (WFI) – pyrogen-free water obtained by • Acetic Acid Irrigation
distillation or reverse osmosis
• Sterile Water for Injection (SWFI) – WFI that has been VII. AEROSOLS
sterilized
• Bacteriostatic Water for Injection (BWFI) – SWFI with • pressurized dosage forms designed to deliver drugs
antimicrobial agent (benzyl alcohol) systematically or topically with aid of a liquefied or propelled
• Sodium Chloride Injection – 0.9% NaCl in WFI gas fire (liquid/ solid drug in a gaseous medium)
b. Non-Aqueous Advantages Disadvantages
• Alcohol • rapid onset of action • environmental concern
• Glycerin • prevents first pass effect • poor inhaler technique
• greater drug stability • risk of oropharyngeal
• Propylene Glycol • fewer systemic side effects deposition
• Polyethylene Glycol • painless and relatively • airway obstruction and
• Fixed vegetable oils (CoCoPeSe) convenient bronchospasms
• Ethyl oleate
• Isopropyl myristate Types of Aerosols

2. Solutes 1. Space Spray

• remain in the air for prolonged periods
a. Active Pharmaceutical Ingredient (API) 2. Surface Spray
• carry the API to a surface
b. Buffers – maintain the required pH of the solution (ex: citrate, 3. Foams
acetate, phosphate) • formed when expansion of propellant within an emulsion
result in production of small bubbles
c. Tonicity Adjusters – reduce the pain of injection (ex: NaCl, Formulation:
dextrose)

d. Preservatives – maintain sterility (ex: thimerosal, benzyl alcohol, 1. Product Concentrate

benzalkonium chloride) • API combined with required adjuncts:
• Surfactant
3. Inert Gas – prevent oxidation of components (ex: Nitrogen Gas) • Antioxidant
• Solvents
Type of Parenteral Injections 2. Propellant
• Gas which develops the pressure within an aerosol and
expels the product when the valve is opened
1. Small-volume Injection – 100 mL or less • Types:
• Packaged in ampoules, vials, prefilled syringes, or minibags • Liquefied Gas – propane, butane, isobutene,
hydrofluorocarbons, dimethyl ether
2. large-volume injection – more than 100 mL • Compressed Gases – CO2, N2, N2O
• Packaged in plastic infusion bags or glass bottes with or
without an air vent tube Parts of an Aerosol
a. Fluid and Electrolyte Replenisher
• Sodium Chloride Injection – 0.9% NaCl
• Ringer’s Injection – NaCl + KCl + CaCl2 1. Pressurizable Container
• Sodium Lactate Injection – systemic alkalinizer • Glass – prone to breakage
• Lactated Ringer’s Injection – NaCl + KCl + CaCl2 + Na • Tin-Plated Steel – most widely
lactate used
• Aluminum – seamless and
b. Fluid and Nutrient Replenisher more inert
• Dextrose Injection 5% (D5W) – most common
• Invert Sugar Injection – dextrose + fructose 2. Valve Assembly – regulates flow
• Amino Acid Injection – for protein synthesis • Actuator – button pressed to
• Mannitol Injection – diagnostic aid in renal function activate valve for emission of
the product
B. OPHTHALMIC • Stern – supports actuator and
delivers formulation in the proper form
• Designed to be instilled onto the external surface of the eye • Gasket – prevents leakage of formulation when the valve is
(topical) or administered inside the eye (intraocular) closed
• May be in the form of solutions, emulsions, suspensions, and • Spring – the mechanism by which the actuator retracts
ointments • Mounting Cup – holds the valve in place
• Problem: Low drug bioavailability • Housing – links the dip tube, stem, and actuator
• Remedy: increase viscosity • Dip Tube – brings the formulation from the container valve
• Example: Eye Mo

Module 5 – Dosage form & Drug Delivery System Page 9 of 9 RJAV 2022
 MODULE 5│PHARMACEUTICS 2

MANUFACTURING PHARMACY
MANUFACTURING PHARMACY Drug Manufacturer

I. INTRODUCTION TO MANUFACTURING 1. Manufacturer – involved in production of drugs products

(preparatory processing, compounding, formulating, filling,
A. MANUFACTUIRNG packaging, repackaging, altering, ornamenting, finishing, labeling)

• large-scale production of drug products’ preparation, 2. Packer – involved in packaging of bulk drug product to its
processing, packaging, labeling, repacking, changing immediate container
wrapper, label or container of any drug products
3. Repacker – involved in repackaging of finished product into
Stages of Manufacturing smaller quantities in a separate container and/ or secondary
packaging

1 2 4 Trader – Registered owner of drug product and formulation but

Dispensing Processing 3 Packaging subcontracts manufacturing
of Raw of Dosage Filling & - Procures RM and PM
Materials Forms Repacking
- Provides monographs and QC protocols

Drug Distributor
Manufacturing Activities
1. Importer – imports RM, API, and/or finished products for
Primary Manufacturing – manufacture of raw material (APIs and wholesale distribution to other licensed established
Excipients)
2. Exporter – exports RM, API, and/ or finished products for
Secondary Manufacturing – manufacture of finished dosage form wholesale distribution to establishments outside the country

Tertiary Manufacturing – packaging, labeling, and repacking of 3. Wholesaler – procures RM, API, and/ or finished
bulk finished product products from a local licensed establishment for local
distribution in wholesale basis
Toll Manufacturing – an arrangement whereby a
competent company manufactures products for another C. DEPARMENTS IN MANUFACTURING COMPANY
company
1. Research and Development Department
B. TYPES OF DRUG ESTABLISHMENTS • formulates new products
• Stages of Drug Development
AO 56 s.1989 1) Discovery and Development
• Revised Regulations for the Licensing of Drug 2) Preclinical Research
Establishments and outlets 3) Clinical Research
4) FDA Review
Drug
Establishments 5) Post-market Surveillance
• involved in process development and scale-up
• prepares Master formula
Drug Drug
Drug Trader Drug Importer Drug Exporter
Manufacturer Wholesaler
Master formula – contains the formulation,
specifications, manufacturing procedures, QA
AO 2014-0034 requirements, and labeling of a finished product
• Rules and Regulations on the Licensing of Establishments
Engaged in the Manufacture, Conduct of Clinical Trial, • justifies overages in the formula
Distribution, Importation, Exportation, and Retailing of Drug
Products, and Issuance of Other Related Authorization Overages – addition of an excess amount of API in
an unstable preparation
Manufacturer
• improves existing products
Packer
Drug 2. Production Department
Manfacturer • deals with all stages of manufacturing batches of finished
Repacker drug products

Trader Batch – specific quantity of product intended to have

uniform character and quality, produced during the
Drug Establishments

Importer same single cycle of manufacture

Drug Distributor Exporter Lot – specific identified portion of a batch

Drugstore Wholesaler • Plans the production according to MO

RONPD
Manufacturing Order (MO) – gives instructions to
manufacture a product
Sponsor
• accomplish the BMR to ensure that batches were properly
made and tests were conducted
CRO
Batch Manufacturing Record (BMR) – document
containing the details of the manufacture of each
batch

Module 5 – Manufacturing Pharmacy Page 1 of 9 RJAV 2022

3. Warehouse Department f. Mannitol and xylitol
• stores materials and finished products • Used in chewable tablets
• holds incoming components in the quarantine area • Negative heat of solution

Quarantine – status of materials which are isolated 2. Binder

physically while a decision is awaited on their release, • Imparts cohesiveness to powders causing them to from
rejection, or reprocessing granules

• involved in purchasing and logistics Inadequate binder Too much binder

4. Quality Assurance Department • Soft granules • Too hard granules
• assures that all operations meet required standards for • Too much fines • Difficulty in screening
safety and efficacy, ensures compliance to cGMP • Inadequately hard tablets • Hampered disintegration &
• conducts quality audit and monitoring dissolution (↓ BA)
• prepares SOPs
a. Starch paste
Standard Operating Procedures (SOP) – step-by- • Binder of choice for wet gran
step instructions for performing operational tasks or
activities b. Acacia & Tragacanth
• Natural guns

5. Quality Control Department c. Gelatin

• tests compliance of raw materials, packaging materials, and • Protein substance
finished products to specifications
• conducts sampling of materials to be tested d. Sucrose
• performs IPQC and environmental testing • Can be used as powder or syrup

6. Marketing Department e. Cellulose Derivatives

• studies current market trends, consumer behavior and • Methyl cellulose
product status in market • Ethyl cellulose
• promote and advertisement • Carboxymethyl cellulose
• Hydroxypropyl methyl cellulose
7. Regulatory Department
• ensures compliance of company and its products with all f. PVP
pertinent regulations and laws about drugs and their • Binder for chewable tablets
marketing
3. Disintegrant
8. Engineering Department • Facilitates the breakup of a tablet when in contact with
• installs, maintains and repairs of equipment and premises aqueous medium
• conducts validation and qualification

Validation – action of proving and documenting that

any process, procedure or method actually and
consistently leads to the expected results
Qualification – action of proving that premises,
systems or equipment work correctly and actually
lead to expected results • MOA:
• Swelling – starch paste
• ensures safety • Wicking – MCC
• Release of gas – effervescent tablets
9. Medical Department
• concerned with physical examination and medical treatment 4. Superdisintegrant
of employees • Newer class of disintegrants which are effective at much
• performs clinical studies lower levels
• publishes house organ/paper • Hydroscopic

II. MANUFACTURING OF SOLID DOSAGE FORMS a. Sodium Starch Glycolate (Explotab®, Primojel®)
• Cross link starch polymer
A. FORMULATION COMPONENTS
b. Crospovidone
1. Diluent (Filler/ Bulking Agent) • Cross link polyvinylpyrrolidone
• inert substance added to increase tablet size or fill the
capsule body c. Croscarmellose Na
• Cross link cellulose derivative
a. Lactose
• Most common 5. Antifrictional Agents (Flow Activators)
• No reaction with most drugs • Fine powders added prior to compression to reduce friction
• Monohydrate, anhydrous, and spray-dried and improve flow properties
• Mostly hydrophobic and added at low concentration
b. Sucrose and Dextrose
• Used as sweetener Lubricant Antiadherent Glidant
Reduces friction Reduces sticking to Reduces friction
c. Microcrystalline Cellulose (Avicel®) between the tablet die walls and picking among particles to
and die wall to by punches enhance the flow
• Good flow and very compressible
facilitate ejection from
• Disintegrates rapidly in water die cavity

d. Starch a. Stearates (Mg, Ca, Na)

• Used as diluent, binder and disintegrant • lubricant, antiadherent and glidant
• Modified Starch: Sta-Rx 1500®, Cellutab®
b. Purified Talc
e. Dibasic calcium Phosphate • lubricant and antiadherent
• Only inorganic salt used as diluent
Module 5 – Manufacturing Pharmacy Page 2 of 9 RJAV 2022
c. Colloidal Talc 1. Dispensing
• glidant • first step in any manufacturing process
• weighing and measuring
d. Colloidal SiO2 (Cab-O-Sil®) • Objective: accuracy of weight → uniform dose
• glidant
Methods:
e. Silicates (Ca and Mg)
• glidant • hand scooping and weighing
• weighing with material lifting assistance
f. PEG and SLS • automated dispensaries
• hydrophilic lubricants
6. Colorant Issues:
• disguises off-color drugs and improves appearance
• weighing accuracy
Dyes Lakes • dust control (dust collecting assistance)
Synthetic organic colorants Dyes adsorbed on an inorganic • lot control of each ingredient
oxide • material movement (WH → DA → PA)
Water-soluble Water-insoluble
Used in solution form Used in fine dispersion or 2. Milling
suspension form
• particle size reduction
• aka sizing, crushing, grinding and pulverization
FD&C Designation Name Color
• Objective: easier and more uniform mixing
Blue No. 1 Brilliant Blue FCF Blue
Blue No. 2 Indigotin Indigo
Methods and its Equipment:
Green No. 3 Fast Green FCF Turquoise
Red No. 3 Erythrosine Pink
Red No. 40 Allura Red AC Red a. Cutting
Yellow No. 5 Tartrazine Yellow • material is cut by means of sharp blades
Yellow No. 6 Sunset Yellow FCF Orange • Cutter Mill – cuts particles using knives; for fibrous materials

7. Flavorant b. Compression
• masks the unpleasant taste of the drug • material is crushed by application of pressure
• End Runner Mill – mortar rotates
a. Salty • Edge Runner Mill – 2 rotating wheels
• cinnamon, orange cherry, butterscotch
c. Impact
b. Bitter • material is hit by an object or it strikes a stationary phase
• chocolate, cherry, raspberry, mint • Hammer Mill – 4 or more hammers hinged on a shaft

c. Sour d. Attrition
• raspberry, lemon, fruity • material is crushed in between rubbing surfaces
• Roller Mill – 2 metal cylindrical rolls rotating
d. Oily
• mint, lemon, orange e. Combined
• Utilizes both impact and attrition methods
e. Unpleasantly sweet • Ball Mill – hollow cylinder containing balls
• vanilla, fruity • Fluid Energy Mill – uses air with very high pressure

8. Sweetener 3. Mixing
• masks the unpleasant taste of the drug • blending materials together into one mass
• Objectives:
Nutritive Non-nutritive • uniform dose
Sugar Alcohols Artificial • even appearance
• Sucrose • Mannitol • Sucralose – 1,000x • avoid segregation
• Fructose • Xylitol • Saccharin – 500x
• Dextrose • Sorbitol • Na Saccharin – 300x Equipment:
• HFCS • Erythritol • Acesulfame K – 180-200x
• Aspartame – 180-200x a. Batch Type Mixer
• Na cyclamate – 30x • all ingredients are loaded together, mixed for a long period,
and discharged as a single batch
B. UNIT OPERATIONS • Rotating Shell/ Tumbling Mixers
• Drum Type Blenders
Tablets HGC • cylindrical-shaped
• rotates horizontally
Dispensing Dispensing • poor cross flow
• remedy: Baffles Slantea
• Double Cone Blender
Milling Milling • conical shaped at both ends
• better cross flow
• Twin-shell/ V-Shell Blender
Mixing Mixing • alternately combines and draws the ingredients
apart
Granulation • solid-solid blending
Granulation
• Fixed Shell Mixers
• Ribbon Blender
Tableting Filling • consists of through-like shell with mounted spiral
or helical blades
• Sigma Blade Mixer
Coating Sealing • consists of double through shaped shell with 2
sigma shaped blades fitted horizontally
• Planetary Mixer

Module 5 – Manufacturing Pharmacy Page 3 of 9 RJAV 2022

 • Paddles moves around its own axis and around
the central axis
• Vertical Impeller Mixer
• Screw type impellers rotating inside a conical shell

b. Continuous Mixer
• agitates and moves materials through equipment, mixing
them in one quick pass
• for high volume products
• materials continuously travel from the charging port to the
discharge nozzle

4. Granulation
• powder size enlargement to granules
• Objective: ↑ flowability and compressibility
Types:

a. Good Granules
• pass through sieve #20 but not through sieve #40 Processes:
b. Fine Granules Slugging
• pass through sieve #40 • formation of slugs
Methods: Roller Compaction
• formation of sheets
a. Wet Granulation
• most common method Equipment:
• addition of liquid binder to powders that forms larger
agglomerates a. Chilsonator roller Compactor
• not for moisture-sensitive and heat labile materials • used to compress powder into thin sheets

b. Oscillating granulator
• used to crushed slugs or sheets into granules

C. MANUFACTURING OF TABLETS

Tableting – compression of materials within a die cavity by the

pressure exerted by the movement of 2 punches

Parts of Tableting Machine:

1. Hopper – holds the materials to be compressed

2. Feed Shoe – transfers materials into die

3. Die – defines size and shape of the tablet

4. Punches – compress materials within the die

5. Cam Tracks – guide the movement of punches

Blending of dry ingredients
Types of Tableting Machine:
Addition of liquid binder Single Station Multiple Station
involves compression of the upper involves movement of both
punch only punches
Screening the damp mass (sieve # 6 or 8)
Requirement of Tableting:

Drying granulation (moisture cnntent: 0.5-1%) 1. Flowability – facilitates transfer

• Problems:
• Arching/Bridging – arch-shaped obstruction forms above
Screening the dry granules (sieve # 12 or 20) hopper outlet
• Rat-Holing – discharge takes place only above hopper
outlets
Addition of running powder
2. Compressibility – forms a stable, compact mass when
*Moisture Content: 31-35%; Underwet – too soft; Overwet – too hard pressure is applied

Fluid Bed Granulation Direct Compression

• easier and faster than the traditional process • tablet processing without granulation
• materials are suspended in air while the liquid binder is • require a very critical selection of excipients →good
sprayed flowability and compressibility; (ex. KCl, NaCl, NaBr;
• diluents: anhydrous/ spray-dried lactose, Avicel®)
2. Dry Granulation
• double compression on pre-compression method
• powder mixture is compacted into large pieces and crushed
subsequently broken down into granules
• for moisture and heat-sensitive materials

Module 5 – Manufacturing Pharmacy Page 4 of 9 RJAV 2022

Tablet Defects 3. Fluid Bed Coater
• air suspension coating or Wurster process
Capping
Types of Coating:
Due to tableting
Lamination
process a. Sugar Coating
• oldest method
Cracking • involves successive coating of sucrose-based solution
• Disadvantages:
• large increase in weight (>50%)
Sticking • time-consuming
Tablet Defects

• requires expertise
Due to excipients Picking Steps:
Color
Sealing Subcoating Smoothing Polishing
coating
Chipping

1. Sealing
Due to Machine Double Impression • waterproofing
• separates tablet core from water
Due to more than 1 • Sealcoating agents
Mottling
factor • shellac
• cellulose acetate phthalate (CAP)
Due to tableting process: • polyvinyl acetate phthalate (PVAP)
• zein
a. Capping
• partial or complete separation of top or bottom crown (air 2. Sub-coating
entrapment) • rounds off the edges and builds up the tablet size
• most critical step
b. Lamination • Sub-coating agents
• separation into 2 or more distinct horizontal layers (air • alternate layers of sticky binder (acacia or gelatin) and
entrapment) dusting powder

c. Cracking 3. Smoothing
• in concave tablets; rapid expansion of tablets • smoothes out the subcoated surface
• Smoothing agents
Due to excipients: • 60-70% syrup

d. Sticking 4. Color coating

• adhesion of material to die wall or face of the punch • Critical step → color and elegance
(excessive moisture) • Color coating agent
• 60-70% syrup + colorant
e. Picking • Steps
• adhesion of material to the design embedded on the punch • Grossing – develops color
tip (excessive moisture) • Heavy Syruping – builds up color
• Regular Syruping – final color
f. Chipping
• removal of small portion of tablet edges (lack of binder) 5. Polishing
• produces gloss/shine
Due to Machines: • Polishing agents
• beeswax,
g. Double Impression • carnauba wax,
• 2 engravings on the surface (due to free rotation of punches • candelila wax
with engraving on faces) • hard paraffin wax
• blending of dry
Due to more than 1 factor:
b. Film Coating
h. Mottling • involves deposition of thin film of polymer around the tablet
• uneven color distribution (due to different color material or core
improper mixing) • Advantages:
• minimal increase in weight (2-3%)
Coating – application of coating material to a moving bed of • easier and faster
solids with concurrent use of heated air
Components:
Methods: Film Former
• produces smooth, thin films
• Pan Pouring – for viscous solutions • examples:
• problem: surface erosion • Non-enteric: celluloses, methacrylate; PVA; PVP
• Pan Spraying – increases efficiency of coating process • Enteric: shellac, CAP, PVAP, salol

Coating Equipment: Plasticizer

• produces flexibility and elasticity
1. Standard Coating Pan • examples:
• consists of a rotating circular metal pan with ducts • castor oil
• (ex. Peilegrini Pan; immersion tube/ sword system) • glycerin

2. Perforated Coating Pan Surfactant

• heated air is exhausted through the perforations in the drum • enhances spreadability of the fil
• (ex. Accela-Cota Pan; Driacoater; Giatt Coater) • example:
• polysorbates (Tween)

Module 5 – Manufacturing Pharmacy Page 5 of 9 RJAV 2022

Alloying Substance • Pin Method/ Reciprocating Die Method – most common
• provides water solubility/ permeability to the film method of manufacturing
• example:
• PEG Steps in filling HGCs:

Glossant Rectification
• Provides luster or shine to the tablets without separate orienting empty shells properly with bodies facing forward
polishing operation
• example: Separation
• beeswax
separation of caps from the bodies
Volatile Solvent/ Vehicle
• allows the spread of the other components over the tablets Filling
• example: dosing of fill material into the body
• alcohol + acetone

Coating Defects: Joining/ Closing

replacement of caps and closing of capsule shells
Mottling
• uneven color distribution
Ejection
• due to poor mixing, uneven spray patterns, or migration of
additives during drying ejection of filled capsules

Sweating Finishing
• oily film or droplets of liquid dedusting and cleaning of surface
• due to humid conditions

Special Techniques:
Bridging
• markings are obscured 1. Sealing
• markings are obscured • Gelatin Banding – seals with a band of gelatin
• due to coating solution filling in the logo of the tablet • Heat Welding – fuses cap to body through double wall
thickness
Erosion • Thermal Coupling – uses liquid wetting agent to lower
• removal of coating from the tablet surface due to friction melting point between cap and body then bonds
among themselves
2. Coating
Cratering • modifies solubility characteristics
• craters appear exposing the tablet surface • (ex. shellac; cellulose acetate phthalate; salol)
• due to disruption of coating at the crown when the surface is
more porous ii. Soft Gelatin Capsules (SGC)
• formed, filled and sealed in a single operation
Blistering
• reduced adhesion and detachment of the film Methods:
• due to entrapment of gases underneath the film
1. Plate Process – oldest method which uses gelatin sheets
Blooming
• fading or dulling of the film 2. Rotary Die Process – uses gelatin ribbons brought together
• due to high concentration and low MW of plasticizer between 2 rotating dies

Blushing 3. Reciprocating Die Process – uses gelatin ribbons brought

• whitish specks or haziness of the film together between 2 rotating dies
• due to precipitation of polymer at high temperature
III. MANUFACTURING OF SEMISOLID DOSAGE FORM
Twinning
• 2 tablets stick together A. MANUFACTURING OF OINTMENTS
• due to inappropriate tablet shape or tracky coating
formulation Methods of Manufacturing

Orange Peel 1. Incorporation

• Rough, non-glossy film surface • the components are mixed until a uniform preparation is
• due to inadequate spreading) attained
• remedy: add polysorbate surfactant • use of ointment roller mills (to mix heat-sensitive ointment
bases), Unguator® Electric Mortar and Pestle
Flaking
• Type I – due to thermal expansion of tablet cores caused by 2. Fusion
over drying • the components are combined by melting together and
• Type II – due to core swelling caused by excessive moisture cooled with constant stirring until congealed
uptake • use of stem-jacketed kettle, ointment roller mill

Delayed Distribution B. MANUFACTURING OF GELS

• associated with the exposure of tablet cores to coating
process conditions rather than a direct effect of the applied Gelling Agents
coating • substances which when added to water or an aqueous
mixture, increase its viscosity
D. MANUFACTURING OF CAPSULES
Types of Gelling Agents:
i. Hard Gelatin Capsules (HGC)
• HGC shells are manufactured in a separate operation from 1. Natural Polymers: alginic acid, gelatin, starch, acacia,
filling tragacanth, Mg Al silicate, bentonite

Module 5 – Manufacturing Pharmacy Page 6 of 9 RJAV 2022

2. Semisynthetic Polymers: cellulose derivatives, sodium starch parabens; methyl – molds (short)
glycolate propyl – yeasts and bacteria (short)

3. Synthetic Polymer: carbomer, polyvinyl alcohol b. Antioxidants

Carbomer – swells in water at basic pH (Carbopol®); neutralized: • prevent oxidation of the active components, fats, and oils
methanol amine
Classification of Antioxidants
Manufacturing Parameters
• the drug and other additives are dissolved in the liquid • True Antioxidants: react with free radicals; alpha tocopherol
vehicle before the gelling agent is added (vit. E), BHT, BHA, alkyl gallates
• Temperature – hot water is preferred for gelatin and PVA • Reducing Agents: ascorbic acid (vit. C), sulfites
and cold water is used for other gelling agents • Antioxidant Synergists: react with heavy metals; EDTA, citric
• Duration of Swelling – 24 to 48 hours acid, tartaric acid
• Removal of Entrapped Air – position the propeller at the
bottom of the container IV.1. MANUFACTURING OF SOLUTIONS

C. FILLING AND PACKAGING A. METHODS

• Usually filled In jars, tubes or syringes 1. Simple Solution

• Jars – plastic or glass • prepared by dissolving the solute in most of the solvent,
• Tubes – plastic laminate or metal mixing until dissolved, then adding sufficient solvent to bring
• Syringes the solution up to the proper volume
• Ointments prepared by fusion should be poured while still • Ex: Calcium Hydroxide Topical Solution, USP
soft directly into the containers
2. Solution by Chemical Reaction
IV. MANUFACTURING OF LIQUID DOSAGE FORMS • prepared by reacting 2 or more solutes with each other in a
suitable solvent
A. EQUIPMENT • Ex: Aluminum Subacetate Topical Solution, USP

1. Mixing Tank – jacketed to allow heating or cooling of contents; 3. Solution by Extraction

Made of stainless • for drugs of vegetable or animal origin
• Grades: • extracted with water or other solvents
• SS 304 – 18% Cr and 8% Ni • Ex: Belladona Extract, USP
• SS 316 – 16% Cr, !0% Ni and 2% Mo; most inert
2. Mixers B. STEPS

Types of Mixers: 1. Dispensing

• weighing and measuring of raw materials
a. Mechanical Stirrer 2. Mixing
• mixers with various impellers mounted on shafts • dissolution of solute in solvent
• problem: vortex formation → remedy: buffers, slanted (45°) • Methods to hasten dissolution
• Vigorous agitation
b. Colloid Mill • Application of heat
• for comminution of solids and dispersion of suspensions • Particle size reduction
• Use of solubilizer and chelating agents
c. Homogenizer 3. Storage and Aging
• compresses liquid with high pressure by a strong spring • for solutions with high amounts of volatile oils; enhances
mechanism odor and flavor
• for emulsification 4. Filtration
• process of separating liquids from solids w/ the use of filter
d. Ultrasonifier medium
• user ultrasonic energy to produce emulsion • Filter Medium – resists the flow of solid materials while
permitting the passage of liquid
B. COMPONENTS • Filter paper
• Membrane filter - sterile products; Bubble Point Test →
1. APIs to test efficiency of membrane filter
2. Solvent or Vehicle • Cotton filter
3. Buffers • Glass-wool filter
4. Viscosity Enhancers • Sintered-glass filter
5. Humectants • Types:
6. Colorants, Flavors, and Fragrances • Parallel Filtration – passes through and filter medium
7. Stability Enhancers • Series Filtration – 2 or more filter media

Stability Enhancers: 5. Filling

• Methods:
a. Preservatives • Gravimetric – large containers and high viscosity
• prevent microbial growth • Volumetric – constant volume using piston action
• effective at low concentration against all possible • Constant-Level – container is used to control fill
microorganisms
IV.2. MANUFACTURING OF EMULSIONS
Classification of Preservatives
A. EMULSIFYING AGENTS
• Alcohols: ethanol, propylene glycol, chlorobutanol, phenyl
alcohol Classification:
• Acids: benzoic acid, sorbic acid
• Esters: parabens 1. Carbohydrate Materials: tragacanth, acacia, agar, pectin,
• Quaternary Ammonium: benzalkonium chloride, cetrimide, chondrus, xanthan, carrageenan
cetylpyridinium chloride
• Organic Mercurial: thimerosal, phenylmercuric nitrate 2. Protein substances: gelatin, egg yolk, casein

Module 5 – Manufacturing Pharmacy Page 7 of 9 RJAV 2022

 B. METHODS
3. Finely Divided Solids: colloidal clay, bentonite, Mg(OH)2,
Al(OH)3; 1. Dispersion
• Finely divided solid drug is wetted first before dispersion in
4. HMW Alcohols: glyceryl monostearate, stearyl alcohol, cetyl the liquid vehicle
alcohol, cholesterol 2. Precipitation
• Finely divided solid drug is reacted with another substance
5. Synthetic Surfactants: • Ex: Milk of Magnesia
• Anionic
• effective at basic pH V. MANUFACTURING OF STERILE DOSAGE FORMS
• ex. soaps; alkyl SO4; sarcosinates
• Cationic A. STERILE PRODUCTIO AREA
• effective at acidic pH
• ex. benzalkonium Cl; cetypyridinium Cl Clean Rooms
• Amphoteric • room in which concentration of airborne particles are
• both anionic and cationic controlled
• ex. betaine; lecithin • Filtered air supplied
• Non-Ionic • positive pressure air flow
• not affected by pH • HEPA filter – removes 99.97% of particles (≥ 0.3 µm)
• Span® – sorbitan esters [lipophilic] from air
• Tween® – polysorbates [hydrophilic • Diocylphthalate Test – QC test for HEPA filter
• Airlocks for entry – space with interlocked doors
HLB Systems
• Stands for hydrophilic-lipophilic balance Classification of Clean Rooms
• Used to categorize surfactants based on the substance’s
polarity US Customary ISO WHO GMP Max no. of particles
• Values range between 1 and 40 per ft3 (≥ 0.3 µm)
• Materials that are highly polar or hydrophilic have been Class 100 ISO 5 Grade A 100
assigned higher numbers Class 1,000 ISO 6 Grade B 1,000
Activity HLB Value Class 10,000 ISO 7 Grade C 10,000
Antifoaming 1-3 Class 100,000 ISO 8 Grade D 100,000
W/O Emulsifier 3-6
Wetting Agent 7-9 B. STERILE MANUFACTURING OPERATIONS
O/W Emulsifier 8-18
Detergent 13-16 Categories
Solubilizer 15-20
1. Terminal Sterilization
B. INSTABILITIES OF EMULSIONS • Prepared, filled and sterilized
• Method of choice whenever possible
1. Creaming – the upward movement of dispersed globules 2. Aseptic Processing
(↑ internal phase) • Components are sterilized separately and assembled

2. Sedimentation – the downward movement of dispersed globules Sterilization Methods

(↓ internal phase)
1. Moist Heat
3. Phase Inversion – an o/w changes to a w/o emulsion or vice • autoclave or steam under pressure (121°C, 15psi, 15-20
versa (w/o ↔ o/w) minutes)
• MOA: protein coagulation
4. Flocculation/ Aggregation – the dispersed globules come • BI: Bacillus stearothermophirus
together but do not fuse 2. Dry Heat
• oven (160-170°C for 2-4 hours)
5. Coalescence – complete fusion of droplets • MOA: oxidation
• BI: Bacillus subtilis
6. Breaking/ Cracking – complete separation of oil and water 3. Membrane Filtration
• membrane filters (0.22 µm); for heat-labile solutions
IV.3. MANUFACTURING OF SUSPENSIONS • MOA: physical separation
• BI: Brevudimonas diminuta
A. FORMULATION 4. Gas
• ethylene oxide, formaldehyde or β-propiolactone
1. Suspending Agents • MOA: alkylation
• Viscosity-increasing agents used to reduce sedimentation • BI: Bacillus subtilis
rate of particles in a vehicle 5. Ionizing Radiation
• Ex: tragacanth, acacia, celluloses, bentonite, magma, • gamma or cathode rays
veegum, agar, carrageenan, gelatin, kaolin) • MOA: DNA mutation
2. Wetting Agents • BI: Bacillus purnilus
• Displace air from cervices of hydrophobic solids to allow
penetration of water Depyrogenation
• Ex: surfactants, glycerin, PPG, PEG, syrup • Oven Settings
3. Flocculating Agents • 180°C for 4 hours
• Reduce the electrical barrier between the particles of the • 250°C for 45 minutes
suspensoid and forming a bridge so as to link them together • 650°C for 1 minute
(decrease zeta potential causing aggregation to avoid
formation of cake) Steps in preparing Sterile Dosage Forms:
• Ex: Electrolytes (NaCl, KCl), surfactants and Polymers
4. APIs 1. Cleaning
5. Liquid Vehicle • Manual cleaning and sterilization of equipment
6. Buffers • Sanitation of clean rooms
7. Preservatives • Sterilization of components for aseptic processing
8. Colorants, Flavors and Fragrances 2. Product Preparation
• Critical process → Class 100

Module 5 – Manufacturing Pharmacy Page 8 of 9 RJAV 2022

 Advantages Disadvantages
• Solutions: dissolution, tonicity adjustment, preservation and - low cost - permeable
filtration - not breakable - low heat resistance
• Dry Solids: spray-drying or freeze-drying (lyophilization) - light weight - not as clear as glass
- chemically inert - poor physical stability
3. Filtration
• Methods b. Multiple Unit
• contains multiple doses and packaged in resealable
• Clarification – 2-3 µm particles
containers
• Cold Filtration – 0.2 -0.3 µm particles
4. Filling • with antimicrobial agent; water: BWFI; USP limit: 30
mL
• Methods
• Gravity Filling – hand-operated • vials
• Pressure filling – semi-automatic
3. According to Material Used
• Vacuum Filling – fully automated
5. Sealing
• Ampoule Sealing a. Glass
• most widely used, made up of inorganic compounds
• Tip-Seal (Bead-Seal) – made by melting the tip of the
neck o an ampoule to form a bead (major component: SiO2)
Advantages Disadvantages
• Pull-Seal – made by heating the neck of a rotating
- rigid and transparent - high cost
ampoule below the tip and pulling the softened glass - impermeable - fragile
away - chemically resistant - relatively heavy
- can be easily sterilized - prone to leaching
VI. PACKAGING AND STORAGE OF DRUG PRODUCTS
Types of Glass
A. PACKAGING I Highly Resistant Borosilicate (Pyrex, Borosil)
Boron – decrease coefficient of expansion
•an economic way of protecting, preparing, identifying, and II Treated Soda Lime Glass
containing the drug products III Soda Lime Glass; Dry Powder Packaging
• composed of container and closure IV/NP General Soda Lime Glass
Types of Packaging: b. Plastic
• organic polymers of HMW
Primary Packaging
• in direct contact with product Types of Plastic:
• immediate container
• affects stability 1. Thermoplastic – soft when heated and hard when
• may provide means of administration cooled; flexible and squeezable
• ex. bottles, caps, liners, filler, desiccant 2. Thermoset – permanently hard; rigid

Secondary Packaging Types of Polymers for Plastic

• outer packaging (not always present)
• encloses primary packaging No. Plastic Use
• ex. carton box, sticker label, inserts, conjugated box 1 Polyethylene Terephthalate - for beverages

2 High-density Polyethylene - hard thermoset for solid

B. CLASSIFICATION OF CONTAINERS
dosage forms
3 Polyvinyl Chloride - for blister packs
1. According to Protection Ability 4 Low-density Polyethylene - thermoplastic for squeeze
bottles and medicine
a. Well-Closed droppers
• protects content from extraneous solids 5 Polypropylene - for autoclave containers
b. Tight
• protects contents from extraneous solids, liquids, c. Metal
and vapors • Used in aerosol cans and collapsible tubes
• protects from deliquescence, efflorescence, d. Foils, Films and Laminates
evaporation • Used in blister packs and strip packs
c. Hermetic e. Rubber
• impervious to air or any other gas • Used in vial stoppers and syringe plugs
d. Light-Resistant f. Paper
• protects from photochemical degradation • Used for divided powders
• amber bottles
e. Child-Resistant C. STORAGE CONDITIONS
• difficult for children under 5 years of age to open
• press down and turn 1. Cold – NMT 2 to 8°C
• squeeze and turn a. Refrigerator – 2 to 8°C
• alight the arrows b. Freezer – -20 to -10°C
• latch top
f. Tamper-Resistant 2. Cool – 8 to 15°C
• uses an indicator which if breached or missing can
provide evidence that tampering has occurred 3. Room Temperature – temperature prevailing in the area
• shrink seal/ wrap
• breakable caps 4. Controlled Room Temperature – 20 to 25°C
• tape seal
• bottle seal 5. Warm – 30 to 40°C
• aerosol → only true temper-resistant packaging
6. Excessive Heat – >40°C
2. According to Quantity Held

a. Single Unit
• contains a single dose only and packaged in non-
resealable containers
• no antimicrobial agent; water: WFI or SWFI; USP
limit: 1000 mL
• ampoules, prefilled syringes

Module 5 – Manufacturing Pharmacy Page 9 of 9 RJAV 2022

 MODULE 5│PHARM 3

PHYSICAL PHARMACY
PHYSICAL PHARMACY • responsible for the solubility of non-polar molecules
• Ex. Iodine complex with salts
• Application of physical chemistry in pharmacy
• Study of physiochemical properties of substances used in PHYSICAL PROPERTIES OF MATTER
drug formulation
Additive
FORCES OF ATTRACTION • depends on the total contribution of the atoms in the
molecules
INTRAMOLECULAR FORCES • Ex. MW, Mass
• ↑ atoms = ↑MW = ↑Mass
• Forces of attraction within the molecule
Constitutive
Types: • depends on the arrangement of the number & kind of atoms
within a molecule
a. Ionic Bond • Ex. Refractive Index, Optical Rotation
• Transfer of electrons between a non-metal & a metal
• observed in formation of salts Colligative
• function of the number of species or particles present in a
b. Covalent Bond given solution
• sharing of electrons between two non-metals • Ex. Osmotic pressure elevation, Vapor Pressure lowering,
• observed in organic compounds Freezing Point Depression, Boiling Point Elevation

INTERMOLECULAR FORCES TYPES OF PROPERTIES

• forces of attraction between molecules Intensive

• independent of the amount of the substance in the system
Types: • Ex. Temperature, Pressure, Density, Viscosity, Surface
tension, Specific Gravity
a. Binding Forces
• Cohesion – similar molecules Extensive
• Adhesion – different molecules • depends on the quantity of substance in the system
• Repulsive – prevent molecules from annihilating each other • Ex. Mass, Length, Volume

b. Attractive Forces STATES OF MATTER

• Van der Waals
• Hydrogen Bond THE GASEOUS STATE
• Ion-Dipole
• Ion-induced Dipole Gas Laws
• refers to an ideal situation where no intermolecular
Van der Waals Forces interactions exist and collisions are perfectly elastic
• weak forces that involve the dispersion of charge across a • there is no energy exchanged upon collision
molecule called a dipole
1. Boyle’s Law
1. Keesom Forces (orientation effect) • relates volume and pressure
• Dipole-dipole • constant temperature
• molecules are polar with permanent polar dipoles • PV = k
• Ex. water, HCl, ethanol, acetone, phenol
2. Gay-Lussac and Charles’ Law
2. Debye Forces (induction effect) • states that the volume and absolute temperature of a gas at
• Dipole-induced dipole constant pressure are directly proportional
• transient dipole induced by a permanent dipole • V = kT
• polar molecules produce temporary electric dipole in
nonpolar molecules 3. Ideal Gas Law
• Ex. Ethyl acetate, methylene chloride, ether • PV = nRT
• R = 0.08205 [Link]/mole.K or 8.314 joules/mole.K or 1.987
3. London Forces (dispersion effect) cal/mole deg
• Induced dipole- induced dipole • n = number of moles
• induce polarity between non polar molecules
• responsible for liquefaction of gases Kinetic Molecular Theory
• Ex. Carbon disulfide, CCl2, hexane • Gases are composed of particles called atoms or molecules,
the total volume of which is so small as to be negligible in
Hydrogen Bond relation to the volume of the space in which the molecules
• electrostatic interaction of H with highly electronegative are confined
atoms (S, N, Cl, F, O) • The particles of the gas do not attract one another, but
• accounts for unusual properties of water instead move with complete independence
• The particles exhibit continuous random motion owing to
Ion-Dipole Interaction their kinetic energy
• polar molecules are attracted to either positive or negative • The molecules exhibit perfect elasticity
charges
• occurs when salt is dissolved in a polar solvent THE LIQUID STATE
• solubility if crystalline substances in H2O
• quaternary ammonium + tertiary amine Critical temperature
• temperature above which a liquid can no longer exist
Ion-Induced Dipole
• induced by close proximity of a charged ion to a non-polar
molecule

Module 5 – Physical Pharmacy Page 1 of 7 RJAV 2022

Critical Pressure Supercritical Fluids
• pressure required to liquefy a gas a critical temperature • properties intermediate between those of liquids and gases
highest vapor pressure of a liquid formed from the gaseous state where the gas is held under a
combination of temperatures and pressures that exceed the
Boiling Point critical point of a substance
• the temp at which the vapor pressure of the liquid equals the
external and atmospheric pressure THE PHASE RULE (GIBB’S PHASE RULE)

THE SOLID STATE • relates the effect of the least number of independent
variables (T, P & C) among the various phases (S, L & G)
• have fixed shapes that can exist in an equilibrium system containing a given
• nearly incompressible number of components 𝐹 =𝐶−𝑃+𝑋
• have strong intermolecular forces Where: F = no. of degrees of freedom
• very little kinetic energy C = no. chemical components
• atoms vibrate fixed positions about an equilibrium position, & P = no. of phases
so there is very little transitional motion X = variable dependent upon considerations of
the phase diagram
Crystalline Solids • F – least number of intensive/independent variables that
• Solids whose structural units are arranged in a fixed must be fixed to describe the system completely
geometric pattern or lattices • C – smallest number of constituents by which the
• definite shape composition of each phase in the system at equilibrium can
• orderly arrangement of units be expressed in the form of a chemical formula or equation
• definite and sharp melting points • P – number of homogenous physically distinct portion of a
• 6 Distinct Critical Systems Based on Symmetry system that is separated from other portions of the system by
• Cubic – Sodium Chloride bounding surfaces
• Tetragonal – Urea • 1 Phase – F=2 – Bivariant
• Hexagonal – Iodoform • 2 Phases – F=1 – Univariant
• Monoclinic – Sucrose • 3 Phases – F=0 – Invariant
• Rhombic – I2
• Triclinic – Boric Acid THERMODYNAMICS

Amorphous Solids • deals with the quantitative relationships of interconversion of

• glasses or supercooled liquids the various forms of energy
• molecules are arranged in a random manner • System – a well-defined part of the universe under study
• no definite melting points • Surroundings – the rest of the universe from which the
• faster dissolution rate observations are made
• Boundaries – physical or virtual barriers that separate a
Polymorphism system from the surroundings
• condition where substances can exist in more than 1
crystalline form TYPES OF SYSTEMS
• polymorphs have different melting points, x-ray crystals and
diffraction patterns and solubility 1. Open – energy and matter can be exchanged with the
• Theobroma Oil Polymorphs (Melting Points) surroundings
• Unstable γ form → 18°C
• α form → 22°C 2. Closed – energy can be exchange with the surroundings but
• β prime form → 28°C not matter
• Stable β form → 34°C
• Types of Polymorphism 3. Isolated – neither matter not energy can be exchanged with
• Enantiotropic – reversible the surroundings
• Monotropic – unidirectional transition
FIRST LAW OF THERMODYNAMICS
Freezing Point
• temperature at which liquid → solid • Energy cannot be created nor destroyed, it can only be
• melting point of a pure crystalline compound transformed into a different form
• Adiabatic – constant heat
Latent Heat of Fusion • Isothermic – constant temperature
• Energy absorbed when 1g of a solid melt • Isochoric – constant volume
• Heat liberated when it freezes • Isobaric – constant pressure

LIQUID CRYSTALLINE STATE SECOND LAW OF THERMODYNAMICS

• liquid crystals → intermediate between liquid and solid states • Refers to the probability of the occurrence of a process
• may result from the heating of solids (thermotropic) or from based on the tendency of a system to approach a state of
the action of certain solvents on solids (lyotropic liquid energy equilibrium
crystals) • Entropy

Two Main Types of Liquid Crystals THIRD LAW OF THERMODYNAMICS

1. Smectic • The entropy of a pure crystalline substance is zero at

• Soap like or grease like absolute zero because the crystal arrangement must show
• molecules are mobile in 2 directions the greatest orderliness at this temperature
• rotates in 1 axis
CONDENSED SYSTEMS
2. Nematic
• threadlike • S & L phases only
• molecules are mobile in 3 directions • the vapor state is disregarded with an assumption of working
• rotates in 1 axis at a pressure at 1atm
• Cholesteric – special type of nematic • 2 Components – liquid phases
• 2 Components – S & L – eutectic mixtures
• 3 Components

Module 5 – Physical Pharmacy Page 2 of 7 RJAV 2022

 TWO COMPONENT SYSTEM CONTAINING TWO LIQUIDS • Bulk Volume – total volume of the material
• Void Volume – difference between bulk and true volume
Binodal Curve
• area within the curve which represent a 2-phase system Density
• True Density – density of actual particle
Upper Consulate/Critical Solution Temperature • Granule Density – volume of particles together with
• maximum temperature at which two phase region in the intraparticulate spaces
phase diagram of a two-component system containing two • Bulk Density
liquids will exist • mass of powder divided by the bulk volume
• USP Method 1 – Graduated Cylinder
Tie line • USP Method 2 – Scott Volumeter
• line from which a system separates into phases of constant • USP Method 3 – Vessel
composition
• approximates proportion of components in a particular Flow Properties
temperature
Conjugate Phases • Angle of Response – maximum angle possible between the
• phases of constant composition that separate when a surface of a pile of power and the horizontal plane
mixture is prepared within the boundary of the 2-phase ℎ
system 𝑡𝑎𝑛𝜃 =
𝑟
Where: h = height of cone
TWO COMPONENT SYSTEM CONTAINING SOLID AND LIQUID r = radius of base cone
• ↑ AOR = ↑ Flow Property
Eutectic Point • Tapped Density – measured using a tapped density tester
• minimum temp. where both exist in liquid form by repeated tapping until a consistent tapped volume is
• point where solid A, solid B & the liquid phase co-exist achieved

THREE COMPONENT SYSTEM LIQUIDS

• Ternary system • less kinetic energy than gases

• 2 liquids that are miscible + 3rd component (co-solvent) with • occupy definite volume
affinity to both layers • take the shape of containers
• has 4 degrees of freedom • denser than gases
• not compressible
MICROMERITICS
SOLUTIONS OF ELECTROLYTES & NON-ELECTROLYTES
• study of small particles
True Solutions
Fundamental properties • molecular dispersions
• defined individually • particle size = <1nm
• Ex. particle size & shape, particle size distribution, surface
area Electrolytes
• form ions in solution
Derived properties • electrical conductance
• computed • Strong Electrolytes
• dependent on fundamental properties • completely ionized in solution
• Ex. Porosity, Density, Flow properties, Packing arrangement • NaCl, HCl, H2SO4
• Weak Electrolytes
PARTICLE SIZE DETERMINATION • partial ionization
• CH3COOH and most drugs
Optical Microscopy
• microscope Non-Electrolytes
• individual particles can be seen • do not form ions in solution
• tedious and 2D image is only seen • no electrical conductance
• Ferret Diameter – measure of the distance between • sucrose, glycerin, urea
tangents parallel to some fixed directions
• Projected Area Diameter – diameter of a circle with the COLLIGATIVE PROPERTY
same area of the particle
• Martin Diameter – length of the line that bisects the particle Vapor Pressure Lowering
• pressure of saturated vapor above a liquid → escape of
Sieving liquid
• use of sieves • molecules
• official method – USP Method • nonvolatile solute + volatile solvent → decreased escape
• mesh number refers to number of openings per inch tendency
• ↑ Mesh Number = ↓ Particle Size (inverse proportionality) • vapor pressure is lowered proportional to relative number of
added solutes
Sedimentation • Ex. Dextrose + Water → ↓VP of water
• Andreasen apparatus
• ↑ Sedimentation rate = ↑ Particle size (direct proportionality) Boiling Point Elevation
• follow the Stoke’s Law • temperature where VP of liquid = external atmospheric
pressure
Particle Size Determination • ↑ non-volatile solute in solution = ↑ BP of solution
• Coulter Counter
• HIAC/Royco Freezing Point Depression
• Gelman Counter • Melting or Freezing Point
• temperature at which S & L phases are at equilibrium
DERIVED PROPERTIES under1 atm
• indicator of purity
Porosity of Voids • Solutions have ↓ FPD than pure substances

• Porosity – measure of a void volume in a powder material

Module 5 – Physical Pharmacy Page 3 of 7 RJAV 2022

Osmotic Pressure Buffer Capacity
• pressure required to prevent the movement of water through • buffer efficiency or buffer index
a semipermeable membrane from region of high to low ∆𝛽
concentration 𝛽=
∆𝑝𝐻
∆B = represents the small increment in gram equivalents per liter of
TONICITY OF SOLUTIONS strong base or acid added to the buffer solution to produce a change
in pH
Isotonic Solutions
• living cell does not gain or loss water SOLUBILITY
• same osmotic pressure with body fluids
• 0.9% NaCl solution, normal saline, D5W • concentration of a saturated solution in which the dissolved
• solute is in equilibrium with its solid phase at constant
Hypertonic Solutions • Intrinsic Solubility
• more solutes compared to cell concentrations • Apparent Solubility
• freeze lower than -0.52°C • Kinetic Solubility
• causes crenation of the cell • Thermodynamic Solubility
• 5% NaCl solution
Factors Affecting Solubility
Hypotonic Solutions • Dissolution Rate of Solute
• less solutes compared to cell concentrations • Temperature
• freeze higher than -0.52°C • Addition of Salt
• causes lysis of the cell • Complex Formation
• distilled water • Salt Formation
• Amorphous Form
Methods of Adjusting Tonicity and pH
Descriptive Term Parts of Solvent for One Part of Solute
Class I Methods Very soluble <1
• NaCl or some other substance is added to the solution of the Freely Soluble 1-10
drug to make it isotonic Soluble 10-30
Sparingly Soluble 30-100
Freezing Point Depression/Crysoscopic Method Slightly Soluble 100-1000
• FPD used to calculate the amount of solute to add in making
an isotonic solution INTERFACIAL PHENOMENON

Class II Methods • attributed to the effect of the properties of molecules located

• water is added to the drug → isotonic solutions or close to the boundary between immiscible phases
• White Vincent Method – V = w x E x 111.1 • Interface – boundary between 2 distinct phases
• Sprowls Method – V = 0.3g x E x 111.1
Surface & Interfacial Tension
THEORIES OF ACIDS AND BASES
Surface Tension
Theory Acid Base • force that pulls molecules of the interface together &
contracts the surface
Arrhenius Liberates H2O in aq. Liberates OH in
solutions aq.
solutions Interface Tension
Bronsted-Lowry Proton donor Proton acceptor • force per unit length existing at the interface
• between 2 immiscible liquids
Lewis Electron acceptor Electron donor
WETTING PHENOMENON
CLASSIFICATION OF SOLVENTS
• contact angle that a droplet of the liquid makes with the solid
• Photophilic (Basic Solvents) – capable of accepting protons • surface at the point of contact
from solute • ↑ Contact Angle θ = ↓ wetting
• Proteogenic (Acidic Solvents) – proton donating • 180° = complete non-wetting
• Aprotic – neither accepts nor donates
SURFACTANTS (SURFACE ACTIVE AGENTS)
Ionization of Weak Acids & Bases
• long chain molecules
• Ionization – complete separation of ions in a crystal lattice • affinity for both polar and non-polar solvents
when a salt is dissolved • reduces interfacial tension
• Dissociation – separation of ions in solution when the ions • based on Hydrophile –Lipophile Balance (HLB) Values
are associated by interionic attraction
Type Description Examples
Henderson-Hasselbalch Equation Anionic Long chain molecules of Sodium lauryl sulfate
• aka pH or buffer equation carboxylates, sulfates or
sulfonates
• preparation of drug solutions at a desired pH using both the
neutral and the salt forms of a drug Cationic Interactions with negatively Benzalkonium chloride
charged surfaces such as cell
• determine percentage of neutral and ionized forms at a given membranes; cytotoxic –
pH antimicrobial preservatives
• determination of pKa of an acid or a base Amphoteric Naturally occurring surfactants Polypeptides, Proteins
𝑠𝑎𝑙𝑡
Weak acids 𝑝𝐻 = 𝑝𝐾𝑎 + 𝑙𝑜𝑔 Zwitterions Alkyl pentanes
𝑎𝑐𝑖𝑑
Lecithin, Cephalins
𝑏𝑎𝑠𝑒 Non-Ionic Long but contains a small Fatty alcohols (lauryl,
Weak bases 𝑝𝐻 = 𝑝𝐾𝑏 + 𝑙𝑜𝑔 alcohol base (e.g., propylene acetyl, stearyl) Steroid
𝑠𝑎𝑙𝑡
glycol), sorbitol or glycerol to alcohols
BUFFERS which fatty acids are attached Glyceryl esters
to form fatty acid esters
• compound or a mixture of compounds which has the ability
to resist changes in pH when small amounts of acids and
bases are added

Module 5 – Physical Pharmacy Page 4 of 7 RJAV 2022

 HLB Values Utilities Examples INSTABILITY OF COARSE DISPERSION
1-3 Antifoaming agent Mineral Oil
Fatty Alcohol Emulsions
Wax • Creaming – upward movement of internal phase
3-6 W/O Emulsifying Agents Span 80
• Sedimentation – downward movement of internal phase
Lanolin • Flocculation – reversible aggregation of droplets
7-9 Wetting & Spreading Agents Brij 30 • Coalescence/Cracking/Breaking – complete fusion of
Docusate sodium droplets (irreversible)
• Inversion – change in the type of emulsion (W/O → O/W or
8-18 O/W Emulsifying Agents Twean 20 O/W → W/O)
Cremophor A25
13-16 Detergents Alkyl Benzenes Suspension
Sulfonates
• Caking – compaction of suspended particles at the bottom of
15-20 Solubilizing Sodium Lauryl Sulfate
the container
ELECTRIC PROPERTIES OF INTERFACES Gels, Jellies, Suppositories & Ointments
• Syneresis – shirking of gel structure caused by loss of liquid
• Nernst Potential – Electro thermodynamic
• Bleeding – liberation of liquid from the base
• Zeta Potential – Electrokinetic • Swelling/Imbibition – absorption of liquid into the structure
• Swelling – increase in volume
COLLOIDAL DISPERSIONS
• Imbibition – no increase in volume
Lyophilic
RHEOLOGY
• Solvent loving
• dispersed phase consists generally or large organic • study of the flow of liquids
molecules lying within a colloidal range
• viscosity is the expression of the resistance of a fluid to flow
• Molecules of the dispersed phase are solvated – they are 𝐹
associated with the molecule comprising the dispersion 𝜂=
medium 𝐺
F = shearing stress (dyne/cm2) – amount of force per unit area
• Spontaneously disperse to form colloidal dispersion required to cause a liquid to flow
• thermodynamically stable G = rate of shear (rev/min) – velocity of the system that leads to
the deformation of the liquid
Association
• Amphiphilic VISCOSITY
• dispersed phase consists of micelles or small organic
molecules or ions whose size individually is below the Units of Measurement
colloidal range • Absolute viscosity – centipoise/poise
• Hydrophilic or lipophilic portion is solvated – depending on • Kinematic viscosity – centistoke/stoke
whether the dispersion medium is aq. or non aq. • Relative viscosity – unitless
• colloidal aggregates are formed spontaneously when the Measurement of Viscosity
concentration of the amphiphile exceeds critical micelle • Capillary Tube Viscometers
concentration • measure the time required for a given volume of liquid
to flow through a capillary
Lyophobic • ↑ Time = ↓ Viscosity
• solvent hating • Ex. Ostwald & Ubbelohde viscometers
• dispersed phase consists of materials that have little • Follows Poiseuille’s Law:
attraction for the dispersion medium 𝜋𝑟 4 𝑡∆𝑃
• material does not spontaneously form a dispersion 𝜂=
8𝑙𝑣
• r = radius of capillary
PROPERTIES OF COLLOIDS
• t = time to flow
• P = pressure in dyne/cm2
Kinetic Properties
• l = length of capillary
• Brownian Movement – particles appear as tiny points of
• v = volume of liquid flowing
light in constant motion
• Diffusion – movement of particles from high to low
• Rotational Viscometers
concentration until equilibrium is achieved
• makes use of a bob or spindle w/c is immersed in the in
the liquid whose viscosity is to be determined
Optical Property
• Rotating Bob – Brookfield, Rotovisco, Stormer
• Tyndall Effect – ability to scatter or disperse light
• Rotating Cup – McMichael
• Faraday Effect
Factors Affecting Viscosity
Electrokinetic Effect
• Temperature
• Electrophoresis – movement of a charged particle through
• ↑T = ↓viscosity in liquids; ↑ in gases
a liquid
• Shear Rate
• Electroosmosis – movement of a liquid through plug or
• Time
membrane across which a potential is applied
• Concentration of Solution
• Sedimentation – creation of a potential when particles
undergo sedimentation
NEWTONIAN SYSTEMS
• Streaming potential -- potential created by forcing a liquid
to flow through a plug or bed of particles
• direct relationship between shearing stress & rate
• constant viscosity with increasing rate
COARSE DISPERSION
• E.g., water, ethanol, acetone, glycerin, benzene
• Emulsion
NON-NEWTONIAN SYSTEMS
• Suspensions
• Semisolid preparations – gels, jellies, suppositories &
a. Plastic Flow
ointments
• Bingham bodies
• curve does not pass through the origin but rather intersects
the shearing stress axis at a particular point (yield value)

Module 5 – Physical Pharmacy Page 5 of 7 RJAV 2022

 • a yield value must be overcome before the system begins to By manipulation of the equation, it can be used to determine the
flow following
• Ex. Flocculated suspension, gels, ointments, pastes, • Pressure
surfactants, polymeric substances • Volume
• Temperature
b. Pseudoplastic Flow • No. of moles
• shear thinning systems • Weight
• curve begins at the origin • Molecular weight
• no yield values • Density
• viscosity decrease w/ increasing shear rate 𝑤𝑡 𝑃𝑉(𝑀𝑊)
𝑛= 𝑤𝑡 =
• Ex. Polymer solution, Na alginate, Perityl cellulose, PEG 𝑀𝑊 𝑅𝑇
𝑤𝑡 (𝑤𝑡)𝑅𝑇
𝑃𝑉 = ( ) 𝑅𝑇 𝑀𝑊 =
c. Dilatant Flow 𝑀𝑊 𝑃𝑉
𝑤𝑡 𝑃(𝑀𝑊)
• shear thickening systems 𝐷= 𝐷=
𝑉 𝑅𝑇
• reverse effects of pseudoplastic flow
• viscosity increases with increases shear rate
Real Gas Equation
• Ex. starch in H2O, conc. suspension of inorganic pigments in
H2O, Zinc Oxide, Barium sulfate or Titanium oxide in H2O
Van der Waal Equation for Real Gases
𝑎𝑛2
Thixotropy (𝑃 + ) (𝑉 − 𝑛𝑏) = 𝑛𝑅𝑇
• decrease in viscosity with time when flow is applied to a 𝑉2
sample previously at rest and the recovery of viscosity in
Where:
time when flow is continued
a/V2 = internal pressure due to IMFA
• Ex. aq. bentonite magma
b = excluded volume
→ accounts for the incompressibility of the gas
Rheopexy NOTE
• refers to the phenomenon that the gel formation of a system Ideal Gas: ↓P, ↑T
may be facilitated by tapping or low shear compared to Real (Non-Ideal) Gas: ↑P, ↓T
keeping the sample at rest
• time dependent increase in viscosity during flow
• Ex. Bovine synovial fluid, serum albumin due to protein, 1 mole of ideal gas
Sodium hyaluronate
𝑃𝑉 = 𝑛𝑅𝑇
Antithixotropy 𝑃𝑉
• time dependent increase in viscosity during flow caused by 𝑛= = 1.0
𝑅𝑇
reversible aggregation of particles
• reversed hysteresis loop Dalton’s Law of Partial Pressure
• Ex. magnesia magma
The total pressure of the system, (PT) is the sum of the individual
GASES partial pressure of each component
• have kinetic energy that produces rapid motion VAPOR PRESSURE OF SOLUTION
• held together by weak intermolecular forces
• capable of filling all available spaces Vapor Pressure
• easily compressible • A measure of escape
Raoult’s Law
GAS LAWS
In ideal solution:
• refers to an ideal situation where no intermolecular
• The partial VP of each volatile constituent is equal to the VP
interactions exist and collisions are perfectly elastic
of the pure constituent multiplied by its more fraction in the
• there is no energy exchanged upon collision
solution
Boyle’s Law Gay-Lussac and Avogadro’s
PA = PA°(XA)
Charles’ Law PB = PB°(XB)
P and V relationship V and T relationship V and n relationship Where: P = partial vapor pressure of solute
(Constant T, n) (Constant P, n) (Constant P, T) P° = vapor pressure of pure solute
Inverse: P ∝ 1/V Direct: V ∝ T Direct: n ∝ V
𝑷𝟏𝑽𝟏 = 𝑷𝟐𝑽𝟐 𝑉1 𝑉2 𝑛1 𝑛2 Graham’s Law
= =
𝑇1 𝑇2 𝑉1 𝑉2
Graham’s Law of Diffusion and Effusion
Combined Gas Law • The speed of diffusion of a gas is relative to the MW or
density of the gas
𝑃1𝑉1 𝑃2𝑉2 1 1
= 𝑟𝑎𝑡𝑒 ∝ 𝑟𝑎𝑡𝑒 ∝
𝑇1 𝑇2 √𝑀𝑊 √𝑑𝑒𝑛𝑠𝑖𝑡𝑦
NOTE: Gay-Lussac’s Law also related to P and T relationship
(Amonton’s Law) 𝑓1 √𝑀𝑊2
=
𝑃1 𝑃2 𝑓2 𝑀𝑊1
=
𝑇1 𝑇2
Henry’s Law
Ideal Gas Laws
• The solubility of gas is directly proportional to pressure at
Ideal Gas Equation constant temperature
• Equation of state of an ideal gas (theoretical gas behaving C=kP ↑P = higher solubility
ideally) Where: C = Concentration of gas in solution
• PV = nRT P = pressure

Module 5 – Physical Pharmacy Page 6 of 7 RJAV 2022

 VAPOR PRESSURE-TEMPERATURE VARIATION

Clausius-Clapeyron Equation
• The relationship between the vapor pressure and the
absolute temperature of a liquid
𝑃2 ∆𝐻𝑣𝑎𝑝 (𝑇2 − 𝑇1)
log =
𝑃1 2.303𝑅𝑇1𝑇2

Where P1 = initial vapor pressure

P2 = final vapor pressure
T1 = initial temperature in K
T2 = final temperature in K
R = gas constant (8.314 J/mol-K
NOTE: the molar heat of vaporization (∆Hvap) is the energy required
to vaporize one mole of a liquid

DRUG PRODUCT STABILITY

• extent to which a preparation retains the same properties

that
• it had at the time of formulation
• It is concerned with:
• Physical Properties
• Chemical Properties and Composition
• Microbiological Sterility
• Therapeutic Activity

Photodegradation
• sensitivity of drug to UV light
• prevention → light resistant / opaque containers

Hydrolysis & Acid-Base Catalysis

• degradation of esters, amides, lactams to carboxylic acid

CHEMICAL KINETICS

REACTION RATES

• may refer to the rate of degradation or formation of a product

from a given reaction
• velocity with which the reaction occurs
• Influenced by:
• Concentration
• Temperature
• Change in pH
• Presence of additives
• Presence of solvents
• Radiation
• Catalytic Agents or Enzymes

ORDER OF REACTIONS

Zero Order
• concentration independent kinetics
• elimination of a reactant will be linear with time
• Ex. suspension

First Order
• concentration dependent reaction
• rate of reaction is proportional to the first power of the
concentration of a single reacting species
• most drugs follow such order of reaction

Second Order
• amount of drug is decreasing at a rate proportional to the
square of the amount of drug remaining
• uncommon

Module 5 – Physical Pharmacy Page 7 of 7 RJAV 2022

 MODULE 5│PHARM JURIS & ETHICS

PHARMACEUTICAL JURISPRUDENCE
PHARMACEUTICAL JURISPRUDENCE / LEGAL PHARMACY 3. A pharmacist serves the needs of the individual, community
AND ETHICS and society and provides health for all.
4. A pharmacist respects the rights of the patients and upholds
Jurisprudence confidentiality of patients’ records.
• Science and philosophy of law 5. A pharmacist acts with honesty, integrity, and
Importance: professionalism in relationship with the patients and other
• To ensure the pharmacist decision and actions are consistent health professionals.
with current legal principles 6. A pharmacist respects the abilities, values and contributions
• To protect pharmacist from liability of colleagues and other health professionals and work with
them closely to ensure better patient care.
Law 7. A pharmacist is committed to continuously enhance
• the sum of rules and regulations by which a society is professional competence.
governed. 8. A pharmacist in coordination with the government and other
health professionals helps in the formulation and
Sources of Law: implementation of health care policies, standards and
programs designed for the benefit of the society
1. Constitution
2. Statutes REGULATION OF PHARMACY PRACTICE
3. Administrative law
4. Common law REPUBLIC ACT NO. 5921

Amendments
• any change in the law can be done by passing this

Ethics
• A method of inquiry that helps people to understand the
morality of human behavior
• The practices or beliefs of a certain group. The expected
standards of moral behavior of a particular group as described • An Act regulating the Practice of Pharmacy and Setting
in the groups formal code of professional ethics Standards of Pharmaceutical Education in the Philippines
and Other Purposes
• Ethical awareness • “Pharmacy Act” or “Pharmacy Law”
• the ability to discern between right and wrong • 23 June 1969
• Ethical competency
• the ability to engage in sound moral reasoning and PRESIDENTIAL DECREE NO. 1363
consider carefully the implication of alternative • Amending Section 18,25, and 39 of RA No. 5921
action • Candidate for board examination (natural born citizen to
Filipino citizen)
Pharmacy ethics • Requirements for the opening of drugstores (natural born
• Refers to the ethical standard and issues that occur in citizen to Filipino citizen)
pharmacy practice • 2 May 1978

Bioethics PRESIDENTIAL DECREE NO. 1926

• Ethics as applied to human life or health • Amending Republic Act No. 5921 (as amend) so as to
reduce the length of the Pharmacy course
Profession • 5 years to not less than 4 years of academic years
• the willingness of an individual practitioner to comply with • 30 May 1984
ethical and professional standard which exceed minimum
legal requirements EXECUTIVE ORDER NO. 174
• Further amending RA No. 5921
Pharmacist • Responsibility for safety, efficacy, quality and purity of drugs
ensure the provision of safe, effective, and quality drugs, for • Deletion of section 29 as a violation of section 40
improved patient care and QOL • Drugs mean (1) article recognized in the current official USP
• 22 May 1987
ETHICAL PRINCIPLE
REPUBLIC ACT NO. 10918
Non-maleficence To do no harm
Beneficence Duty to promote good
Respecting the professional relationship
patient
Respect for autonomy Respect for the individual’s right to decide on
issues that affect self
Consent Right to be informed and to choose a course of
action
Confidentiality right to give or refuse consent relative to Republic Act No. 10918 ([Link])
release of privileged information • Act regulating and modernizing the practice of Pharmacy in
Respect for persons the Philippines
Veracity obligation to tell the truth, or honesty • “Philippine Pharmacy Act”
• Repealed Republic Act No. 5921
THE PHILIPPINE PHARMACISTS’ ASSOCIATION CODE OF • Lapsed into law on 21 July 2016 without the signature of the
ETHICS President in accordance with Article VI, Section 27 (1) of the
Philippine Constitution
1. A pharmacist places the well-being of the patient at the • 47 years to repeal RA No. 5921
center of professional practice. • 16 years in the making – first draft of the Pharmacy bill was
2. A pharmacist promotes the welfare of everyone in a caring presented in 2000
and compassionate manner.

Module 5 – Jurisprudence Page 1 of 9 RJAV 2022

5 Presidents of the Philippine Pharmacists Association: • Good Clinical Practice, which are deemed vital in the
• Dr. Lourdes Echauz performance of their roles and functions in different practice
• Dean Eladio Tinio areas.
• Ms. Normita Leyesa
• Dean Leonila Ocampo Definition of Terms – As used in this Act:
• Dr. Olivia Limuaco a) Accredited Professional Organization
b) Adult vaccines
10 Chairpersons of the Professional Regulatory Board of c) Adulterated/ Deteriorated pharmaceutical products
Pharmacy: d) Biopharmaceuticals
• Hon. Edelweiss Mallari e) Brand name
• Hon. Virginia Barros f) Cipher, Code or Secret Key
• Hon. Marian Andaluz g) Compounding
• Hon. Catalina Sanchez h) Continuing Professional Development
• Hon. Reynaldo Umali i) Cosmetics
• Hon. Jennifer Flores j) Counterfeit pharmaceutical product
• Hon. Marilyn Tiu k) Dangerous Drugs
• Hon. Mildred Oliveros l) Dispensing
• Hon. Aldrin Santiago m) Drugs
• Hon. Adelina Royo n) Emergency cases
o) Expiration date
3 Congresses: p) Filling
• 14th, 15th, 16th q) Food/ Dietary Supplements
r) Generic name
Objectives – This Act provides for and shall govern the: s) Health supplement
a) Standardization and regulation of pharmacy education; t) Household remedies
b) Administration of licensure examination, registration, and u) Institutional pharmacies
licensing of pharmacists; v) Internship program
c) Supervision, control, and regulation of the practice of w) Label
pharmacy in the Philippines; x) Labeling materials
d) Development and enhancement of professional competence y) Medical device
of pharmacists through continuing professional development, z) Medical mission
research, and other related activities; and aa) Medicines
e) Integration of the pharmacy profession. bb) Medical representative or professional service representative
cc) Nontraditional outlets
Scope of the Practice of Pharmacy – A person is deemed to be dd) Online pharmacy services
practicing pharmacy, within the meaning of R.A. No. 10918, when ee) Over-the-counter medicines
with or without a fee, salary, percentage or other rewards, paid or ff) Pharmaceutical establishments
given directly or indirectly. gg) Pharmaceutical manufacturers
• Activities exclusive to pharmacists hh) Pharmaceutical marketing
a) Prepare, compound or manufacture, preserve, store, ii) Pharmaceutical outlets
distribute, procure, sell, or dispense, or both, any jj) Pharmaceutical products
pharmaceutical product or its raw materials; or kk) Pharmacist
b) Render services, such as clinical pharmacy services, ll) Pharmacist only OTC medicines
drug information services, regulatory services, mm) Pharmacy aides
pharmaceutical marketing, medication management, or nn) Pharmacy assistants
whenever the expertise and technical knowledge of the oo) Pharmacy technicians
pharmacist is required; or pp) Philippine Practice Standards for Pharmacists
c) Engage in teaching scientific, technical, or professional qq) Physician’s sample
pharmacy courses in a school or college of pharmacy; rr) Prescription/ Ethical medicines
or ss) Refilling of a prescription
d) Dispense pharmaceutical products in situations where tt) Referral
supervision of dispensing of pharmaceutical products is uu) Referral registry
required; vv) Refresher program
i) Provide other services where pharmaceutical ww) Telepharmacy
knowledge is required.
• Activities non-exclusive to pharmacists THE PROFESSIONAL REGULATORY BOARD OF PHARMACY
e) Chemical, biological or microbiological analyses and
assay of pharmaceutical products, food/dietary • under the administrative control and supervision of the PRC,
supplements, health supplements, and cosmetics; or • composed of a chairperson and two (2) members,
f) Physico-chemical analyses for medical devices used in • appointed by the President of the Philippines
aid of administration of pharmaceutical products; or • Exercise administrative, quasi-legislative, and quasi-judicial
g) Administration of adult vaccines as approved by the power.
Food and Drug Administration (FDA): Provided, That
they shall undergo the training on the safe Qualifications of the Chairperson and Members of the Board
administration of adult vaccines and management of a) Be a citizen of the Philippines and a resident for at least five
adverse event following immunization (AEFI) for (5) years;
pharmacists and hold a certificate of training issued by b) Be a duly registered and licensed pharmacist in the
an institution duly accredited by the Professional Philippines, preferably a holder of a masteral degree in
Regulation Commission (PRC); Provided, further, That Pharmacy, or its equivalent;
the safe administration of vaccines be part of the higher c) Have been in the active practice of pharmacy for the past ten
education curriculum for pharmacists; or (10) years;
h) Conduct or undertake scientific research in all aspects d) Have not been convicted of a crime involving moral turpitude;
involving pharmaceutical products and health care e) Be a member in good standing of the APO for at least five (5)
years, but not an officer or trustee thereof; and
All pharmacists are expected to abide by current standards f) At the time of appointment, must neither be a member of the
such as: faculty nor an administrative officer of any school, college or
• Philippine Practice Standards for Pharmacists, university offering degree programs in pharmacy nor has any
• Good Laboratory Practice, direct or indirect pecuniary interest or connection in any
• Good Distribution Practice, review center or similar institution.
• Good Manufacturing Practice and

Module 5 – Jurisprudence Page 2 of 9 RJAV 2022

Hon. Anthony Aldrin C. Santiago Grounds for Suspension or Removal from Office of the
• Officer in Charge (as of August 2020) Chairperson or Member of the Board
Hon. Milred B. Oliveros a) Gross neglect, incompetence, or dishonesty in the discharge
• Member of duty;
Hon. Adelina C. Royo b) Involvement in the manipulation, tampering, or rigging of the
• Member licensure examination, its questions or results, or both, and
in the disclosure of classified and confidential information
Incumbent Chairperson and Members of the Board shall, in an pertaining to the licensure examination;
interim capacity to function as such until the new Board, created c) Conviction of an offense involving moral turpitude by a court
under RA 10918 shall be appointed and qualified. of competent jurisdiction; and
- (Sec. 49, RA 10918) d) Unprofessional, unethical, immoral, or dishonorable conduct.

Powers, Functions, and Responsibilities of the Board EXAMINATION, REGISTRATION, AND LICENSURE
a) Administer and implement the provisions of this Act;
b) Promulgate rules and regulations, administrative orders, and Qualifications for the Licensure Examination
issuances necessary to carry out the provisions of this Act; a) A citizen of the Philippines or of a foreign country which has
c) Prepare licensure examination questions, score, and rate the a law or policy on reciprocity for the practice of the pharmacy
examinations and submit the results thereof to the PRC. The profession;
Board shall prepare, adopt, issue, or amend the syllabi or 1. Certified of Live Birth
tables of specifications of the subjects in the licensure 2. Married female: Certificate of Marriage
examination, in consultation with the academe and the 3. NBI Clearance
Commission on Higher Education (CHED); b) Of good moral character and reputation;
d) Recommend the issuance, suspension, revocation, or c) A degree holder of Bachelor of Science in Pharmacy or its
reinstatement of the COR, PIC or Special/Temporary Permits equivalent degree conferred by an HEI in the Philippines or
(STP) for the practice of pharmacy; an institution of learning in a foreign country duly recognized
e) Administer oaths in accordance with the provisions of this by the CHED;
Act; 1. Certified true copy of the Transcript of Records in
f) Regulate and monitor the practice of pharmacy in the Bachelor Science in Pharmacy
Philippines, including the practice of subprofessional d) Has completed an internship program approved by the
services such as pharmacy technicians, pharmacy Board, pursuant to such guidelines as may hereinafter be
assistants, aides, and other medicine handlers, as described promulgated, in consultation with the duly recognized
in this Act; adopt measures that may be deemed proper for associations of pharmacy schools and the CHED.
the enhancement of the profession and the maintenance of
high professional, academic, ethical, and technical Certificate of Registration (COR) as Pharmacist Is issued subject
standards; and conduct ocular inspection of pharmaceutical to following conditions:
establishments and higher education institutions (HEIs), in • Passed the licensure examination
coordination with concerned government agencies; • Compliance with the registration requirements
g) Promulgate and prescribe the Pharmacists’ Code of Ethics, • Payment of the prescribed fees
Code of Technical Standards and Guidelines for the This COR shall remain in full force and effect until suspended or
Professional Practice of the Pharmacy Profession, in revoked in accordance with RA No. 10918
coordination with the APO;
h) Represent the pharmacy profession in all fora involving Personal Identification Card (PIC) bearing the registration number
concerns and issues related to pharmaceutical products and and dates of its issuance and expiry, duly signed by the Chairperson
the practice of pharmacy; of the PRC
i) Investigate cases arising from violations of this Act, the rules • PIC shall be renewed every three (3) years, upon
and regulations promulgated pursuant thereto, the presentation of:
Pharmacists’ Code of Ethics, Code of Technical Standards • Certificate of Good Standing (COGS) from the APO
and Guidelines for the Professional Practice of the Pharmacy • Proof of completion of the CPD requirements.
Profession, and other Board issuances;
j) Delegate the hearing or investigation of administrative cases Continuing Professional Development (CPD)
filed before the Board, except where the issue or question • Inculcation of advanced knowledge, skills, and ethical values
involves the practice of the profession, in which case, the in a post-licensure specialized or in a n inter- or
hearing shall be presided over by at least one (1) member of multidisciplinary field of study for assimilation into
the Board, to be assisted by a Legal or Hearing Officer of the professional practice, self-directed research, and/or lifelong
PRC; learning.
k) Conduct, through the Legal Officers of the PRC, summary • Mandatory requirement in the renewal of the Professional
proceedings on minor violations of this Act, the General Identification Cards of registered and licensed pharmacists.
Instruction to the Examinees, including the implementing (Sec. 20, RA No. 10918)
rules and regulations issued by the Board, and to render
summary judgment thereon which shall, unless appealed to Reissuance of Revoked Certificate of Registration
the PRC, become final and executory after fifteen (15) days • The Board may, upon petition, reinstate or reissue a revoked
from receipt of notice of judgment or decision; COR after the expiration of two (2) years from the date of its
l) Issue and promulgate guidelines on CPD, in coordination revocation.
with the APO;
m) Recommend the accreditation of the standardized training Replacement of Lost or Damaged Certificate of Registration,
programs for and certifications of medical representatives or Professional Identification Card or Special/Temporary Permit.
professional service representatives, pharmacy technicians, • A duplicate copy of the COR for display in Category B
pharmacy assistants, pharmacy aides and other medicine establishments may be issued.
handlers covered in Section 39, Article IV of this Act. The • Replacement of lost or damaged COR, PIC or STP may be
Board shall promulgate the criteria and guidelines in the issued in accordance with the pertinent rules that shall be
accreditation of training programs and certifications as issued thereon.
described above, in coordination with the APO and with other
concerned government agencies; REGULATION OF THE PRACTICE OF PHARMACY
n) Accredit Specialty Boards of Pharmacy based on the criteria
that it shall establish and prescribe; and Affixing RPh After a Registered Pharmacist’s Name – Only duly
o) Perform and discharge such other functions and registered and licensed pharmacists shall have the right to affix to
responsibilities, as may be deemed implied, incidental, and one’s name, the title "Registered Pharmacist" or "RPh"
necessary, to preserve the integrity of the pharmacy
licensure examination and to enhance and upgrade the Indication of Information – A pharmacist shall be required to
practice of the pharmacy profession in the country. indicate the serial numbers, the date of expiry of the pharmacist’s

Module 5 – Jurisprudence Page 3 of 9 RJAV 2022

PIC and APO Certificate of Membership on all pertinent documents b) Category B – where the supervision and oversight of a duly
signed by him/her. registered and licensed pharmacist is required.
1. Retail outlets selling household remedies and OTC
Registry of Pharmacists – The Board and the PRC shall prepare drugs as differentiated from the pharmacist-only OTC
and maintain a registry of medicines;
• Names 2. Satellite institutional pharmacies providing medicines
• Residences or office addresses or both solely to employees of their respective companies or
• Status of registration the employees’ qualified dependents, or both; or
Updated annually, in coordination with the APO. This registry shall members of a duly registered organization or institution;
be made available to the public upon inquiry or request, subject to 3. Fourth, fifth and sixth class municipal health units
such guidelines that shall be established involved in the procurement, distribution, dispensing,
and storage of pharmaceutical products;
Display of Certificate of Registration – every pharmacist engaged 4. Institutions providing telepharmacy services; and
in the practice, whether in private or under the employ of another, to 5. Nontraditional outlets of pharmaceutical products:
display the original copy of one’s COR in a prominent and Provided, That no prescription medicines and
conspicuous place in the drug establishment in which one is pharmacist-only OTC medicines are sold.
employed in a professional capacity as pharmacist. When employed
in establishments under Category B, as defined in Section 31 of this A pharmacist working in a Category A establishment may be allowed
Act, the duplicate copy of the pharmacist’s COR shall also be to simultaneously work or render pharmacy services in Category B
displayed therein. - No pharmacist shall knowingly allow the COR to establishments, the maximum number of hours of which shall be
be displayed in an establishment where one is not actually employed determined, in accordance with such guidelines as may be
as a professional pharmacist. established therefor by the Board, in coordination with the FDA, and
Any person who shall commit this act, upon conviction, be other agencies, establishments, institutions, and regulatory bodies.
sentenced to pay a fine or not less than Php 250,000.00 but not
exceeding Php 500,000.00 OR imprisonment of not less than one Procurement, storage, distribution, or dispensing of any
(1) year and one (1) day but not more than six (6) years, or both, at pharmaceutical product in the national government and local
the discretion of the court (Sec. 45 (b), RA 10918) government units shall be made only under the supervision of a duly
registered and licensed pharmacist.
Dispensing/Sale of Pharmaceutical Products – No
pharmaceutical product, of whatever nature and kind, shall be All units or sub-units of establishments, institutions, and regulatory
compounded, dispensed, sold or resold, or otherwise be made bodies whether government or private with functions and activities
available to the consuming public, except through a retail drug outlet that are exclusive for pharmacists, as defined in Section 4,
duly licensed by the FDA. (Sec. 45 (f), RA 10918) paragraphs (a), (b), (c), (d) and (i), shall be headed and managed by
• Prescription drugs and pharmacist-only OTC medicines shall a qualified duly registered and licensed pharmacist
be dispensed only by a duly registered and licensed
pharmacist, except in emergency cases, where the services Responsibility for Quality of Pharmaceutical Products – Duty of
of a registered and licensed pharmacist are not available: a duly licensed and registered pharmacist of a pharmaceutical
Provided, that a report shall be made to the supervising establishment and outlet to ensure that all pharmaceutical products
pharmacist within twenty-four (24) hours after the occurrence conform to standards of safety, quality and efficacy, as provided for
of the emergency so that product recording in the in this Act and other pertinent rules and regulations and issuances.
prescription books can be done. Owners, managers, or pharmacists in charge of the operation of
• A registered and licensed pharmacist may refuse to pharmaceutical establishments and outlets shall be held jointly
compound, dispense or sell drugs and pharmaceutical responsible for nonconformance with these standards.
products, if not in accordance with this Act and the
abovementioned standards. (Sec. 45 (j), RA 10918) In cases of pharmaceutical products sold in their original package,
• Licensed manufacturers, importers, distributors, and the seal of which has not been broken or tampered with, the liability
wholesalers of pharmaceutical products are authorized to that may arise because of their quality and purity rests upon the
sell their products only to duly licensed pharmaceutical manufacturer or importer, the distributor, representative, or dealer
outlets. (Sec. 45 (d), RA 10918) who is responsible for their distribution or sale.

Pharmacist Requirement – Establishments/outlets which are Physician’s Sample – Pharmaceutical products given or intended
required to employ and/or retain and maintain the professional to be given free to any health professional by a manufacturer or
services of duly registered and licensed pharmacists: distributor or its professional service representative as part of its
a) Category A – where the direct and immediate control and program or promotion shall not be sold to any pharmaceutical outlet
supervision of a duly registered and licensed pharmacist is or the consuming public.
required, per establishment, whether in-store or online
1. Selling or otherwise making available to the consuming Pharmaceutical products classified as antimicrobials, including anti-
public prescription/ethical medicines, combination TB medicines and other classifications of medicines, as may be
products (medical device and drugs) classified as drugs prescribed by the FDA, shall not be given or distributed as
according to the primary intended mode of action, physician’s samples.
pharmacist-only OTC medicine, whether owned by the
government or by a private person or firm, whether sold Handling of Pharmaceutical Products by Persons Other Than a
at wholesale or retail; Pharmacist – For the purpose of this section, persons handling
2. Manufacture, importation, exportation, distribution, and pharmaceutical products, other than the pharmacist, which shall
sale of combination products (medical device and include:
drugs) classified as drugs according to the primary • pharmacy owners who are non-pharmacists,
intended mode of action; • medical representatives or professional service
3. Departments/Divisions/Units of pharmaceutical representatives,
laboratories, pharmaceutical manufacturing • pharmacy support personnel,
laboratories, or other establishments with processes • pharmacy technicians,
involving the preparation, manufacture, assay, • pharmacy assistants,
regulation, product research and development, quality • pharmacy aides,
control, repacking, importation, exportation, distribution, • persons who assist pharmacists in any part of a pharmacy
sale or transfer of pharmaceutical products in quantities operation,
greatly in excess of single therapeutic doses; and • persons performing functions involved in the handling of
4. Government units, including local government, city, first pharmaceutical products,
to third class municipal health units, nongovernment • shall be duly certified by appropriate government agencies
organizations and/or associations involved in the after undergoing an accredited training program.
procurement, distribution, dispensing and storage of
pharmaceutical products

Module 5 – Jurisprudence Page 4 of 9 RJAV 2022

No person, except pharmacy graduates, shall be allowed to render its Equipment, augmenting its Human Resource
such services without undergoing a comprehensive standardized Complement, Giving Authority to Retain its Income,
training program: Provided, That the job description is defined in the renaming it the Food and Drug Administration (FDA),
implementing rules and regulations of this Act. amending certain sections of RA No. 3720, as amended.
• “Food and Drug Administration Act of 2009”
Administration of Adult Vaccines • 18 August 2009
• licensed and trained pharmacist who shall administer adult • Creation of FDA in the DOH
vaccines shall ensure that the vaccine to be administered • FDA Centers shall be per major product category:
shall have a doctor’s prescription which is not more than 1. Center for Drug Regulation and Research – including
seven (7) days old veterinary medicine, vaccines, and biologicals
• submit a monthly vaccination report and AEFI report to DOH 2. Center for Food Regulation and Research
regional offices using the prescribed form. 3. Center for Cosmetics Regulation and Research –
including household hazardous/ urban substance
ACCREDITED PROFESSIONAL ORGANIZATION 4. Center for Device Regulation, Radiation Health and
Research
Integrated and Accredited Professional Organization (IAPO) of • FDA Centers shall regulate the manufacture, importation,
Pharmacists exportation, distribution, sale, offer for sale, transfer,
• A pharmacist duly registered with the Board shall promotion, advertisement, sponsorship of, and/or, where
1. automatically become a member of the integrated and appropriate, the use and testing of health products
accredited professional organization of pharmacists, • Each Center shall be headed by a Director. The Centers will
and have at least of the following divisions:
2. receive the benefits and privileges appurtenant thereto 1. Licensing and Registration Division
upon payment of the required fees and dues. 2. Product Research and Standards Development
• Membership shall not be a bar to membership in other Division; and
associations of pharmacists. 3. Laboratory Support Division
• FDA Offices and Center:
Membership to the Integrated and Accredited Professional 1. The Administration and Finance Office headed by
Organization the deputy director-general for administration and
• All pharmacy support personnel must be registered as finance shall have, at least, the following divisions: the
affiliate members of the APO and Human Resource Development Division; Property and
• maintain membership throughout the duration of employment Logistics Management Division; Human Resource
in pharmaceutical establishments and outlets. Management Division; Assets and Financial
Management Division; and the Information and
Specialty Boards in Various Areas of Pharmacy Practice – Communication Technology Management Division.
Specialty Boards in various areas of pharmacy practice shall be 2. The Policy and Planning Office which shall be under
created, subject to accreditation by the Board and the PRC. The the Office of the Director-General shall have, at least, a
Board shall issue guidelines in the accreditation of specialty boards training, advocacy and communications division and
in various areas of pharmacy practice shall monitor the performance of the centers for product
research and evaluation and standards development.
FOOD, DRUGS, COSMETICS AND DEVICES REGULATION 3. The Field Regulatory Operations Office headed by
the deputy director-general for field regulatory
REPUBLIC ACT NO. 3720 operations shall include, among others, all the field
offices, field or satellite laboratories and the regulatory
enforcement units.
4. The Legal Services Support Center shall provide
legal services to the entire FDA and shall be directly
under the Office of the Director-General."

Reminders: Keep yourself updated especially COVID-19

([Link] and/or FDA Official Facebook page)
• An Act to Ensure the Safety and Purity of Food, Drugs and
cosmetics Being Made Available to the Public by creating the DANGEROUS DRUGS REGULATION
Food and Drug Administration which shall administer and
enforce the laws REPUBLIC ACT NO. 6425
• “Food, Drugs and Devices, and Cosmetics Act”
• 22 June 1963

EXECUTIVE ORDER NO. 851

• Reorganizing the Ministry of Health, Integrating the
Components of Health Care Delivery into its Field Operations
• Creation of Bureau of Food and Drugs which shall assume
the functions of the Food and Drug Administration which is
abolished • “The Dangerous Drugs Act of 1972”
• 2 December 1982 • 30 March 1972

EXECUTIVE ORDER NO. 175 REPUBLIC ACT NO. 9165

• Further amending RA No. 3720
• 22 May 1987

REPUBLIC ACT NO. 9711

• An Act instituting the Comprehensive Dangerous Drugs Act

of 2002, repealing Act No. 6425, known as the Dangerous
Drugs Act of 1972
• An Act Strengthening and Rationalizing the Regulatory • “Comprehensive Dangerous Drugs Act of 2002”
Capacity of the Bureau of Food and Drugs by Establishing • 7 June 2002
Adequate Testing Laboratories and Field Offices, upgrading
Module 5 – Jurisprudence Page 5 of 9 RJAV 2022
 UNLAWFUL ACTS AND PENALTIES 2nd offense: 6 mos 50,000 –
and 1 day to 12 200,000
UNLAWFUL ACT IMPRISONMENT FINE (in years
pesos) Cultivation or culture of plants Life imprisonment 500,000 –
Importation of dangerous drugs Life imprisonment 500,000 – classified as dangerous drugs to death 10,000,000
to death 10,000,000 Failure to comply with the One year and one 10,000 –
Importation of controlled precursor Twelve years and 100,000 – maintenance and keeping of the day to six years 50,000
and essential chemical one day to twenty 500,000 original records of transactions of *revocation of
years any dangerous dug or controlled license to practice
Protector/ Coddler of any violator of Twelve years and 100,000 – precursor in case of
the provisions under Sec. 4 one day to twenty 500,000 practitioner
years •
Sale, administer, dispense and Life imprisonment 500,000 – Unlawful prescription of dangerous Life imprisonment 500,000 –
transport dangerous drugs to death 10,000,000 drugs to death 10,000,000
Sale, administer, dispense and Twelve years and 100,000 – Unnecessary prescription of Twelve years and 100,000 –
transport controlled chemical one day to twenty 500,000 dangerous drugs one day to twenty 500,000
years years
Maximum penalty if:
• Sale is within 100m from school DANGEROUS DRUGS TEST AND RECORD REQUIREMENT
• For drug pushers who use minors or mentally incapacitated
individuals as runner, couriers and messengers The following shall be subjected to undergo drug testing:
• If the victim of the offense is a minor or a mentally incapacitated a) Applicants for driver's license (mandatory)
individual
• If the offense is the proximate cause of death
b) Applicants for firearm's license and for permit to carry
• If a person organizes, managers act as a “financier” firearms outside of residence (mandatory)
Maintenance of a den, dive, or Life imprisonment 500,000 – c) Students of secondary and tertiary schools (random)
resort of dangerous drugs to death 10,000,000 d) Officers and employees of public and private offices
Maintenance of a den, dive, or Twelve years and 100,000 – (random)
resort of controlled chemicals one day to twenty 500,000 e) Officers and members of the military, police and other law
years enforcement agencies (mandatory)
Maximum penalty if: f) All persons charged before the prosecutor's office with a
• Sold to a minor who is allowed to use the same in such a place
criminal offense having an imposable penalty of
• Any person who organizes, manages or act as a financier of any
illegal activities imprisonment of not less than six (6) years and one (1) day
shall have to undergo a mandatory drug test; and
- Should any dangerous drug be the proximate cause of death of a g) All candidates for public office whether appointed or elected
person using such den, dive or resort the penalty of death and a both in the national or local government shall undergo a
fine ranging from PhP1,000,000 to PhP15,000,000 shall be mandatory drug test.
imposed on the maintainer, owner and/or operator
Employees and visitors of a den, Twelve years and 100,000 –
Accreditation of Drug Testing Centers and Physicians
dive r resort one day to twenty 500,000
years • The DOH shall be tasked to license and accredit drug testing
Manufacture of dangerous drugs Life imprisonment 500,000 – centers
to death 10,000,000 • The DOH shall also accredit physicians who shall conduct
Manufacture of controlled precursor Twelve years and 100,000 – the drug dependency examination of a drug dependent as
and essential chemical one day to twenty 500,000 well as the after-care and follow-up program for the said drug
years dependent.
Manufacture or delivery of Twelve years and 100,000 – • The DOH shall establish, operate and maintain drug testing
paraphernalia for manufacture of one day to twenty 500,000 centers in government hospitals
dangerous drugs years
Inject, ingest, or inhale or introduce Six months and 10,000 –
into human body a dangerous drug one day to four 50,000 Records Required for Transactions on Dangerous Drug and
years Precursors and Essential Chemicals
Possession of Dangerous Drugs Twelve years and 100,000 – • Every pharmacist dealing in dangerous drugs and/or
- 10 g or more of opium; one day to twenty 500,000 controlled precursors and essential chemicals shall maintain
- 10 g or more of morphine; years and keep an original record of sales, purchases, acquisitions
- 10 g or more of heroin; and deliveries of dangerous drugs, indicating therein the
- 10 g or more of cocaine or following information:
cocaine hydrochloride;
- 50 g or more of
1. License number and address of the pharmacist;
methamphetamine 2. Name, address and license of the manufacturer,
hydrochloride or "shabu"; importer or wholesaler from whom the dangerous drugs
- 10 g or more of marijuana have been purchased;
resin or marijuana resin oil; 3. Quantity and name of the dangerous drugs purchased
- 500 g or more of marijuana; or acquired;
4. Date of acquisition or purchase;
10 g or more of other dangerous
drugs such as, but not limited to,
5. Name, address and community tax certificate number of
methylenedioxymethamphetamine the buyer;
(MDA) or "ecstasy", Para 6. Serial number of the prescription and the name of the
methoxyamphetamine (PMA), physician, dentist, veterinarian or practitioner issuing
trimethoxyamphetamine (TMA), the same;
lysergic acid diethyl amine (LSD), 7. Quantity and name of the dangerous drugs sold or
gamma hydroxy amphetamine delivered; and
(GHB), and those similarly designed
or newly introduced drugs and their
8. Date of sale or delivery.
derivatives, without having any • A physician, dentist, veterinarian or practitioner authorized to
therapeutic value or if the quantity prescribe any dangerous drug shall issue the prescription
possessed is far beyond therapeutic therefor in one (1) original and two (2) duplicate copies
requirements, as determined and • All prescriptions issued by physicians, dentists, veterinarians
promulgated by the Board in or practitioners shall be written on forms exclusively issued
accordance to Section 93, Article XI by and obtainable from the DOH.
of this Act
Possession of dangerous drugs Graduated Graduated
below 10grams penalties fines DANGEROUS DRUGS BOARDS AND PHILIPPINE DRUG
Possession of Equipment, Maximum penalties Maximum ENFORCEMENT AGENCY
Instrument, Apparatus and Other provided in Sec. 11 fines
Paraphernalia for Dangerous Drugs of RA No. 3165 The Dangerous Drugs Board – The Board shall be the policy-
Use of dangerous drugs 1st offense: min. of - making and strategy-formulating body in the planning and
6 mos. Rehab formulation of policies and programs on drug prevention and control.

Module 5 – Jurisprudence Page 6 of 9 RJAV 2022

Composition of the Board – The Board shall be composed of REPUBLIC ACT NO. 9994
seventeen (17) members wherein three (3) of which are permanent
members, the other twelve (12) members shall be in an ex officio
capacity and the two (2) shall be regular members.
• The three (3) permanent members, who shall possess at
least seven-year training and experience in the field of
dangerous drugs and in any of the following fields: in law,
medicine, criminology, psychology or social work, shall be
appointed by the President of the Philippines.
• An Act Granting Additional Benefits and Privileges to Senior
Philippine Drug Enforcement Agency (PDEA) – implementing arm Citizens, further amending RA No. 7432
of the Board, and shall be responsible for the efficient and effective • “Expanded Senior Citizens Act of 2010”
law enforcement of all the provisions on any dangerous drug and/or • 22 June 2010
controlled precursor
• The PDEA shall be headed by a Director General with the REPUBLIC ACT NO. 10366
rank of Undersecretary, who shall be responsible for the
general administration and management of the Agency. The
Director General of the PDEA shall be appointed by the
President of the Philippines and shall perform such other
duties that may be assigned to him/her.
• The two (2) deputies director general shall likewise be
appointed by the President of the Philippines

REPUBLIC ACT NO. 10586 • An Act Authorizing the Commission on Elections to establish
precincts assigned to accessible polling places exclusively
for persons with disabilities and senior citizens
• 15 February 2013

REPUBLIC ACT NO. 10645

• An Act Penalizing Persons under the Influence of Alcohol,

Dangerous Drugs, and Similar Substances
• “Anti-Drunk and Drugged Driving Act of 2013”
• 27 May 2013

SOCIAL LEGISLATION • An Act providing for Mandatory PhilHealth Coverage for all
senior citizens, amending RA No. 7432, as amended by RA
REPUBLIC ACT NO. 7432 No. 9994.
• 5 November 2014
• An Act to Maximize the Contribution of Senior Citizens to
Nation Building, Grant Benefits and Special Privileges and REPUBLIC ACT NO. 6675
for Other Purposes
• 23 April 1992

Senior citizen – Any resident of the Philippines at least 60 years

old, including those who have retired from both government offices
and private enterprises, and has an income of not more than sixty
thousand pesos per annum subject to review by NEDA every three
years
• An Act to Promote, Require, and Ensure the Production of
An Adequate Supply, Distribution, use and acceptance of
REPUBLIC ACT NO. 7876
drugs and medicines identified by their Generic Names
• “Generics Act of 1988”
• An Act Establishing a Senior Citizens Center in all cities and
• 13 September 1988
municipalities of the Philippines
• “Senior Citizens Act of Philippines”
Generic Drug – drug not covered by patent protection and which
• 14 February 1995
are labeled solely by their international non-proprietary name (INN)
Center – place established by this Act with recreational, educational,
The Use of Generic Terminology for Essential Drugs and
health, and social programs and facilities designed for the full
Promotional Incentives
enjoyment and benefit of the senior citizens in city or municipality.
• The exclusive use of generic terminology in the manufacture,
marketing and sales of drugs and medicines, particularly
REPUBLIC ACT NO. 9257
those in the Essential Drugs List

Who Shall Use Generic Terminology

a) All government health agencies and their personnel
b) All medical, dental and veterinary practitioners, including
private practitioners, shall write prescriptions using the
generic name. The brand name may be included if so
desired.
• An Act Granting Additional Benefits and Privileges to Senior c) Any organization or company involved in the manufacture,
Citizens amending RA No. 7432 importation, repacking, marketing and/or distribution of drugs
• “Expanded Senior Citizens Act of 2003” and medicines shall indicate prominently the generic name of
• 26 February 2004 the product.
d) Drug outlets

Module 5 – Jurisprudence Page 7 of 9 RJAV 2022

 REPUBLIC ACT NO. 9502 vegetables and fruits; locally manufactured instant noodles; coffee;
sugar; cooking oil; salt; laundry soap and detergents; firewood;
charcoal; household liquefied petroleum gas (LPG) and kerosene;
candles; drugs classified as essential by the Department of Health
and such other goods as may be included under Section 4 of this
Act.

Prime Commodities – are goods not considered as basic

necessities but are essential to consumers in times of any of the
• An Act Providing for Cheaper and Quality Medicines, cases provided under Section 7 of this Act such as, but not limited
amending for the purpose RA No. 8293, RA No. 6675 and to, flour; dried, processed or canned pork, beef and poultry meat;
RA No. 5921 dairy products not falling under basic necessities; onions, garlic,
• “Universally Accessible Cheaper and Quality Medicines vinegar, patis, soy sauce; toilet soap; fertilizer, pesticides and
Act of 2008” herbicides; poultry, livestock and fishery feeds and veterinary
• 6 June 2008 products; paper; school supplies; nipa shingles; sawali; cement;
clinker; GI sheets; hollow blocks; plywood; plyboard; construction
Drugs and Medicines Price Monitoring and Regulation Authority nails; batteries; electrical supplies; light bulbs; steel wire; all drugs
of the Secretary of the Department of Health not classified as essential drugs by the Department of Health
• DOH Secretary has the power to recommend the maximum
retail price of drugs and medicines subject to price regulation REPUBLIC ACT NO. 7581
(Sec 23 List of Drugs)
• President of the Republic of the Philippines Approves Illegal Acts of Price Manipulation

Display of Maximum Retail Price Fixed and Approved by Order • Hoarding – undue accumulation by a person or combination
of the President of the Philippines for Drugs and Medicines of persons of any basic commodity beyond his or their
Subject to Price Regulation normal inventory levels or the unreasonable limitation or
• "RETAIL PRICE NOT TO EXCEED" preceding it, and refusal to dispose of, sell or distribute the stocks of any basic
"UNDER DRUG PRICE REGULATION" on a red strip. necessity or prime commodity to the general public
• Profiteering - the sale or offering for sale of any necessity or
Maximum Retail Price (MRP) – government initiated prime commodity at a price grossly in excess of its true worth
Government Mediated Access Price (GMAP) – private sector • Cartel - it is a combination of agreement between two or
more persons engaged in the activity of any basic commodity
CONSUMER PROTECTION designed to artificially and unreasonably increase or
manipulate the price
REPUBLIC ACT NO. 8203 • Panic buying - abnormal phenomenon where consumers
buy necessities and prime commodities grossly in excess of
• An Act Prohibiting Counterfeit Drugs their normal requirement resulting in undue shortages of
• “Special Law on Counterfeit Drugs” such goods to the prejudice of less privilege
• 5 September 1996
MUST KNOWS
Counterfeit drugs – Correct ingredients but not on the amounts
provided, wrong ingredients, without active ingredients, with Amendments/
sufficient quantity of active ingredients, active ingredient is less than RA No. Common name Year supplemental
80% of labeled amount, fake trademark, not registered with the FDA AOS
EO 174 RA
RA 5921 Pharmacy Law June 23, 1969
Parties liable for counterfeit medicines: 9502
• Manufacturer EO 175
• Importer Food, Drugs and AO 55
RA 3720 June 22, 1963
• Seller Cosmetics Act AO 56
RA 9711
• Distributor
• Manager AO 62
Generics Act of September 13,
• Operator of laboratory RA 6675 AO 63
1988. 1988
RA 9502
• Pharmacist
Special Law on
RA 8203 July 22, 1996
Counterfeit Drugs
REPUBLIC ACT NO. 7581
The Dangerous
RA 6425 April 4, 1972 RA 9165
Drugs Act of 1972."
• An Act Providing Protection to Consumers by Stabilizing the
Comprehensive
Prices of Basic Necessities and Prime Commodities against RA 9165 Dangerous Drugs June 7, 2002 None
undue increases during Emergency situations and like Act of 2002"
occasions Senior Citizen Act of
RA 7432 April 23, 1992 RA 9257
• “Price Act” 1992
• 27 May 1992 Expanded Senior
RA 9257 February 26, 2004 RA 9994
Citizens Act of 2003
REPUBLIC ACT NO. 10623 RA 9994
Expanded Senior
February 15 2010
Citizens Act of 2010
Consumer Act of
RA 7394 April 13 1994
the Philippines
RA 7581 Price Act May 7, 1992
Universally
Accessible Cheaper
RA 9502 and Quality June 6, 2008
Medicines Act of
• An Act Amending Certain Provisions of RA No. 7581 2008
• 6 September 2013 Food and Drug
RA 9711 Administration August 18, 2009
(FDA) Act of 2009
Basic Necessities – are goods vital to the needs of consumers for
"Traditional and
their sustenance and existence in times of any of the cases provided Alternative Medicine
under Section 6 or 7 of this Act such as, but not limited to, rice, corn, RA 8423 December 9, 1997
Act (TAMA) of
root crops, bread; fresh, dried or canned fish and other marine 1997."
products; fresh pork, beef and poultry meat; fresh eggs; potable
water in bottles and containers; fresh and processed milk; fresh
Module 5 – Jurisprudence Page 8 of 9 RJAV 2022
Pharmacy Law commonly asked concepts and definition

a. Cipher vs. Codes vs. Secret keys

Cipher Codes Secret keys

method of secret system of words or characteristics style or
writing that other systems symbols kept from the
substitutes other arbitrarily used to knowledge of others
letters or characters present words or disclosed
for the letter confidentially to one or
intended few

b. Authorities to memorize

President of the the members of the board of pharmacy are

Philippines- appointed by
Council of to recognize and accredit colleges and school of
pharmaceutical pharmacy in the different universities is a function
education of
Board of pharmacy to reprimand any erring pharmacist or to suspend
or revoke his certificate of registration
BFAD the minimum mandatory requirements necessary
for the opening and operation of drugstores are as
prescribed by

c. Important numbers to memorize

21 years ‒ the minimum age requirement to

practice pharmacy in the Philippines
5 years ‒ the book kept for the purpose of
recording the sale of violent poisons
should preserved in the period of
‒ ordinary prescription shall be retained
by the pharmacist for a period of
‒ number of years of pharmacy practice
for the pharmacist to comply as board
examiner
60 days ‒ the decision of board of pharmacy in
administrative cases involving
pharmacist becomes final and
executor
2 ‒ members of the board and a
chairman- composition of board of
pharmacy
‒ times board exam is given in a year
960 hours ‒ complete pharmacy internship
program
10 days ‒ the BOP, upon receipt of formal
complaint under oath against any
pharmacist, shall furnish an answer
within

Module 5 – Jurisprudence Page 9 of 9 RJAV 2022

c. High Performance Liquid Chromatography (HPLC) 4. Iodine Value
• Widely used and preferred current assays of biological and • grams of iodine absorbed by 100g of sample
pharmaceutical product • quantitative measure of unsaturated fatty acids
• SP: column packed with glass or plastic beads coated with
silica derivatized with nonpolar functional group Classification
• MP: liquid pumped through the column with high pressure Drying oil Semidrying oil Nondrying oil
• Reverse-phase: water, methanol, acetonitrile Iodine Value > 120 100-120 < 100
• Normal-phase: hexane, diethyl ether Examples Linseed oil Cottonseed oil Olive oil
Cod liver oil Sesame oil Almond oil
d. Gas Chromatography • Methods:
• Used to analyze volatile substance • USP Method I: Hanus Method – iodobromide TS
• SP: either a solid adsorbent or liquid ion an inert support • USP Method II: Wijs Method – iodochloride TS
• MP: chemically inert carrier gas (helium or nitrogen) • Unofficial Method: Hubl Method – HgCl2 + I2
• Formula:
2. Partition Chromatography 𝑁 𝑥 (𝑉𝑏 − 𝑉𝑎)𝑥 0.1269
𝐼𝑉 = 𝑥 100
• Based on partition between 2 immiscible solvents 𝑊𝑡𝑠𝑎𝑚𝑝𝑙𝑒
• Both SP and MP are in liquid form
Sample Problem
a. Paper Chromatography Determine the iodine value of an unknown sample of oil weighing
• SP: water molecules bound to the cellulose of the filter paper 0.17g if 36mL and 17mL of 0.1100N of sodium thiosulfate are
• MP: nonpolar or hydrophobic solvent required for the blank and residual titration respectively
0.11 𝑥 (36 − 17)𝑥 0.1269
3. Ion Exchange Chromatography 𝐼𝑉 = 𝑥 100 = 𝟏𝟓𝟔
0.17
• Used for the separation of charged molecules (ions) based
their binding to fixed charges on a support C. ASH AND MOISTURE CONTENT DETERMINATION
• Uses:
• Most effective method for water purification 1. Ash Content
• Separation of amino acids • Residue left after incineration of an organic material which
• SP: employs either a cationic or an anionic exchanger which represents the amount of inorganic impurity
is capable of exchanging counter ions in the surrounding
medium in a reversible process Types:
Total Ash
4. Permeation Chromatography • Residue after incinerating at 325 ± 25℃
• Molecules are separated according to their size by their Acid-Insoluble Ash
ability to penetrate a sieve-like structure • Residue after boiling the total ash with 3N HCl and igniting
• Ex: Size Exclusion Chromatography the remaining insoluble matter
Water-Soluble Ash
5. Affinity Chromatography • Difference in weight between total ash and residue after
• Utilized highly specific interactions between one kind of treatment of total ash with water
solute molecule and a second molecule covalently attached
to the SP Temperature Equivalence:
• Ex: protein affinity chromatography Flame Color Temperature ℃
Very dull red 500-550
IV. SPECIAL METHODS Dull red 550-700
Bright red 800-1000
A. ASSAY OF VOLATILE OILS Yellow red 1000-1200
White 1200-1600
1. Alcohol
• acetalization method 2. Moisture Content
• Methods:
2. Aldehyde and Ketone • Method I – Karl Fischer Titrimetry
• bisulfite method (Cassia flask) or hydroxylamine method • Method II – Azeotropic Distillation
(titration) • Method III – Gravimetry

3. Phenol D. NITROGEN CONTENT DETERMINATION

• KOH method (Cassia flask)
𝑉𝑠𝑎𝑚𝑝𝑙𝑒 − 𝑉𝑟𝑒𝑠𝑖𝑑𝑢𝑎𝑙 Kjeldahl Method
%𝑃ℎ𝑒𝑛𝑜𝑙 = 𝑥 100 • For quantitative determination of nitrogen in organic
𝑉𝑠𝑎𝑚𝑝𝑙𝑒
substance.
4. Volatile Oil in Spirit
• Babcock bottle • Conversion of Organic N into NH4+ by adding H2SO4
Digestion
Sample Problem
In phenol content determination of a volatile oil, the insoluble layer in
• Conversion of NH4+ into ammonia
the graduated neck of the Cassia flask reached 3.1mL which is
Distillation
obtained from a sample of 10mL after treatment with KOH solution.
The percentage of phenol sample is:
• Titrating with sulfuric acid
10𝑚𝐿 − 3.1𝑚𝐿 Titration
%𝑃ℎ𝑒𝑛𝑜𝑙 = 𝑥 100 = 𝟔𝟗%
10𝑚𝐿

B. ASSAY OF FATS AND FIXED OILS

1. Acid Value
• mg of KOH needed to neutralize free acids in 1g of sample
2. Ester Value
• mg of KOH needed to saponify the esters in 1g of sample
3. Saponification Value/ Koettstorfer Number
• mg of KOH needed to neutralize and saponify the esters in
1g of sample 𝑆𝑉 = 𝐴𝑉 + 𝐸𝑉

Module 6 – Qualitative & Quantitative Analysis Page 6 of 6 RJAV 2022