Integrated Physical Pharmacy &

Pharmaceutics I

By Abrham S.

INTRODUCTION TO IPP-I 1
Reference
Books

INTRODUCTION TO IPP-I 3
 Chapters
.1. Introduction to dosage forms
2. Phase Equilibria

Content 3. Interfacial Phenomena

4. Solubility and Distribution
5. Packaging and storage of drugs (assi)
6. Pharmaceutical Solutions
7. Rheology
8. Colloids
9. Pharmaceutical Suspensions
10. Pharmaceutical Emulsions
INTRODUCTION TO IPP-I 4
  Introduction to dosage
Chapter One forms
 Definitions, the need for dosage forms
 Introduction to pharmaceutical ingredients
 Routes of administration
What is the
difference
between Drug
& Medicine?

INTRODUCTION TO IPP-I 6
Introduction
Pharmaceutical sciences

Pharmaceutics Pharmacology Clinical

pharmacy

Pharmaceutical Social Pharmacy

Pharmacognosy Chemistry

Physical
Biopharmaceutics
Pharmacy

Industrial
Pharmacokinetics
Pharmacy

INTRODUCTION TO IPP-I 7
Introduction…

Physical Pharmacy Pharmaceutics

Integrated Physical Pharmacy & Pharmaceutics

INTRODUCTION TO IPP-I 8
What is Physical Pharmacy?
 The study of the physical and chemical properties of drugs and their

dosage forms
 The applications of physics and chemistry to the study of pharmacy

INTRODUCTION TO IPP-I 9
What is Pharmaceutics?
 Pharmaceutics is concerned with the scientific and technological

aspects of the design, development and manufacture of dosage

forms
Drug

 the science of dosage form design Pharmaceutics

Medicine

INTRODUCTION TO IPP-I 10
What is Pharmaceutics?
 Drug
pharmacologically active ingredient

medicinal agent

‘pharmacological agent’, ‘active principle’, ‘active

ingredient’,
‘therapeutic’ or ‘active pharmaceutical ingredient (API
 Medicine
Dosage forms, drug-delivery systems

Drug + Excipient

INTRODUCTION TO IPP-I 11
What is Pharmaceutics?...
 Pharmaceutics is the most diverse of all subject areas in

Pharmaceutical science and encompasses:

 Understanding of the basic physicochemical properties of the drug

and additives (Physical pharmacy)

 The design and formulation of medicines (dosage form design)
 Selecting route of administration and right dosage form

 Selection of excipients (type and amount)

 Assessment of compatibility

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What is Pharmaceutics?
 Stability studies

 Biopharmaceutical and pharmacokinetic studies

 Process development and scale up

 The manufacturing of these medicines on both small scale

(compounding) and a large scale (pharmaceutical technology )

INTRODUCTION TO IPP-I 13
What is Pharmaceutics?....
 Relevant body systems and how drugs arrive there following

administration
Biopharmaceutics
 The avoidance and elimination of microorganisms in medicines
Pharmaceutical microbiology
Sterilization
 Product performance testing
Dissolution testing,
drug release, stability testing

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Dosage forms (DF)
 Drugs are not administered as such and they are converted into a
palatable form, which is called as “dosage form.”
 a preparation devised to make possible the administration of
medications in a measured or prescribed amount.

 They are drug delivery systems. i.e. a means of administering

drugs to the sites of action within the body in a safe, efficient,
reproducible and convenient manner

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Major considerations in the
DF
 The physicochemical properties of the drug itself.
 particle size and surface area

 solubility, dissolution, partition coefficient

 crystal properties, stability, organoleptic properties and others

 Biopharmaceutical considerations
 how route of administration and type of dosage form affects rate
and extent of absorption

INTRODUCTION TO IPP-I 16
Major considerations in the DF…
 Therapeutic considerations of the disease state
 the most suitable type of dosage form

 possible routes of administration

 the most suitable duration of action and dose frequency for the

drug in question

INTRODUCTION TO IPP-I 17
Reasons for converting drugs to dosage form
1. To provide the mechanism for the safe and convenient delivery of
accuracy of dose
2. To mask bad odor and taste of drugs, e.g. coated tablets, flavored
syrup
3. To protect the drug from external environment
4. To protect the drug from internal environment
5. To provide liquid preparations of substances that are either
insoluble or unstable in the desired vehicle

INTRODUCTION TO IPP-I 18
  Based on routes of administration
Route Dosage forms
Oral Solutions, suspensions, emulsions, gels, powders, granules,
capsules, tablets
Rectal Suppositories, ointments, creams, powders, solutions
Vaginal pessaries, tablets, capsules, solutions, creams, sprays, ointments,
foams
Topical Ointments, creams, pastes, gels, solutions , aerosols
Parenteral Injections (solutions, suspension, emulsion), implants, irrigations
and dialysis solutions
Respiratory Aerosols (solution, suspension, emulsion, powder), inhalations,
sprays, gases
Nasal Solutions, inhalations
Eye Solutions, ointments, creams
Ear Solutions, suspensions, ointments, creams
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INTRODUCTION TO IPP-I 20
 Routes of drug administration
 It is one of the factors that should be

considered during dosage form design

Routes of drug
administration  The most common routes of drug
administration are

 Oral route  The vaginal route

 oral cavity  Topical route
 The rectal route  The nasal route
 Parenteral route  Inhalation

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Routes of drug administration

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 Oral route
(peros)
 Most frequently used
 Simplest, most convenient and safest route of administration
 Usually for systemic use but some times for local effect in the GIT

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Disadvantages of oral route
 Slow onset of action
 Irregular absorption(inter-& intra-individual variability) & destruction
 Interaction with foodstuffs
 variation in gastric emptying
 disease conditions
 personal variations

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Disadvantages of oral route….
 Destruction of some drugs by enzymes and other secretions of GIT
 First pass/pre-systemic metabolism (by enzymes in the GIT/liver)
 Unsuitable for unconscious or vomiting patients and for immediate

pre- or post operative use and incases of malabsorption states

INTRODUCTION TO IPP-I 25
 The Buccal
routes of the drug into
 Administration
the oral cavity

 Can be used for both systemic

and local action

 Two sites for absorption of

drugs from the buccal cavity

INTRODUCTION TO IPP-I 26
The Buccal routes….
i. Sublingual ii. Buccal absorption
absorption
 The area under the tongue  the medicament is placed
 Fast onset of action but the between the cheek & the gum
duration is usually short  Quick onset of action and can

also give a longer duration of

action

INTRODUCTION TO IPP-I 27
Advantages
 Relatively quick onset of action
 Drugs are absorbed systemically, there by
avoiding the ‘first pass effeect’

 Drugs can be administered for unconscious patients

 Because the tablet is not swallowed

 The drugs for this route are usually formulated as tablets, sprays and

gels

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Advantages…
 The patient should be made aware of the difference between the

two sites and should be given full instruction on how to administer

the drugs to ensure maximum benefit

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 The rectal route
 Administration of a drug into the rectum where the drug is released

to give local or systemic effect

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Advantages
 Can be used when the oral route is unsuitable (in cases of)
 Severe vomiting, unconscious patients

 Uncooperative patients such as children, elderly or mentally

disturbed and patients with dysphagia

 Useful when the drug causes GIT irritation
 Can be used for local action (eg. Treatment of hemorrhoids)

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Advantages….
 Can be used for drugs which are inactivated by GIT enzymes and

secretions
 avoids pre-systemic metabolism (partially)

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Disadvantages
 Absorption is irregular and unpredictable, giving rise to variable

effect.
 Slow absorption (low fluid volume and low surface area)
 Less convenient than oral route
 Low patient acceptability
 Large dose is required (50% more than oral route)

INTRODUCTION TO IPP-I 33
 The vaginal route
 Most often for local effect
 However, drugs absorbed form this route are not subjected to the

first pass effect

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❺Parenteral route
 Drugs are injected via a hollow tube into the body at various sites

and varying depths.

 The preparations should be sterile

The three main parental routes are:

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Parenteral
route ….

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i. intravenous (IV)
 Drugs are injected directly into the systemic circulations (veins).
 Produces the fastest onset of action

INTRODUCTION TO IPP-I 37
ii. Intramuscular (IM)
 Drugs are injected into muscle layers
 Produce a fairly fast action when the drug is formulated as

aqueous solution
 A slower and more prolonged action will be obtained when the
drug is formulated in oily vehicle or as suspension

INTRODUCTION TO IPP-I 38
iii. Subcutaneous route
 Drugs are injected to the subcutaneous layer of the skin
 Easier and less painful

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Other less frequently used parenteral routes
 Intracardiac
 intrathecal
 intrarterial, etc

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Advantages of parenteral ROA
 Rapid onset of action (rapid absorption, directly into systemic

circulation)
 Prolonged effect can be obtained (depot)
 Useful in emergency situations
 Can be used for vomiting, unconscious and uncooperative patients
 Used for GIT irritant drugs
 For drugs which are destroyed, inactivated, or poorly absorbed
form GIT

INTRODUCTION TO IPP-I 42
Disadvantages
 Inconvenient and less patient acceptance
 Expensive, Tissue damage
 Painful (there is trial of needle free injections)
 Reversal of toxicities is difficult

INTRODUCTION TO IPP-I 43
❻Topical route
 Drugs are applied on the skin
 Common dosage forms: powders, liquids, semisolids
 Reasons for application
 for local effect (disease treatment, cosmetic purpose, protection)
 For systemic effect (Very rare)

֍ The application of drugs to other topical sites, such as eye and ear
are also included under this route.
֍ Ophthalmic preparations should be sterile

INTRODUCTION TO IPP-I 44
❼The nasal route
 Has been traditionally used for producing local effects using

solutions as drops or sprays.

 More recently, it has been used for systemic action because of its

good vascular supply which avoids first pass metabolism although it

does have local enzyme activity

INTRODUCTION TO IPP-I 45
❽Inhalation/respiratory/
route of drugs through mouth or nose into the lung
 Administration
 Predominantly used for local administration to treat respiratory

conditions such as asthma.

 Drugs are delivered directly to the site of action in low dose with a
consequent reduction in side effects.

INTRODUCTION TO IPP-I 46
❽Inhalation/respiratory/
 Butroute….
there could be systemic toxicities because of high absorption
from lungs (high surface area of alveoli, high blood flow).
 Because of the high blood flow and large surface area
drug absorption from this route is extremely rapid

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Common Routes of Drug
administration

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Common Routes of Drug
administration

INTRODUCTION TO IPP-I 49
  Introduction to Pharm. ingredients

Pharmaceutical  Solvents (vehicle)

excipients  Preservatives
 Antioxidants
 Buffering Agents
 Viscosity enhancing agents
 Isotonicity modifiers
 Surface-active agents
 Sweetening & coloring agents

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Introduction
֍ Drug substances are seldom administered alone
 given as part of a formulation, in combination with one or more

nonmedical agents
 known as pharmaceutical ingredients or excipients

֍ The word “excipient” is derived from Latin word

“excipere”, meaning ‘ to except‘-'other than‘

֍ Any component of a drug product other than an active ingredient

added intentionally to the medicinal formulation
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 Introduction….
 Conventionally/ideally, excipients should be inert
 Modern excipients however modulate:
 Solubility

 Bioavailability

 drug delivery to the site of action, etc;

API Excipient Dosage Form

INTRODUCTION TO IPP-I 52
Roles of conventional and Novel DD
excipients
Therapeutics Compliance
 Effectiveness  Pharmaceutical elegance
 Safety  Appearance
 Reliability  Organoleptic properties
 Stability
 Physical  Convenience
 Chemical  Ease of use
 Microbiological  Dosing frequency
 Control release and  Consumer
 Drug targeting acceptance

INTRODUCTION TO IPP-I 53
Properties of pharmaceutical
excipient
 safe
 no harmful or toxicological effect
 physiologically inert
 no instability
 with drug substance, other excipients in the formulation & primary
packing materials
 ease of accessibility
 inexpensive

INTRODUCTION TO IPP-I 54
❶Solvents (vehicle)
 Medium in which active and other ingredients are dispersed
 Choice of the vehicle depends on:
 The intended use of the preparation

 Physicochemical properties of the drug

 Compatibility, Stability, Cost , etc

INTRODUCTION TO IPP-I 55
Water as a vehicle
Vehicle of choice for most pharmaceutical ingredients
 Widely available,

 Relatively inexpensive

 Palatable (free of dis-agreable taste and smell)

 Non-toxic for internal use,

 Non-irritant for external use

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Water as a vehicle …
 Limitations
 Non-selective

 Solubility limit

 Hydrolytic degradation of ingredients

 Microbial contamination/growth

INTRODUCTION TO IPP-I 57
i. Potable water
 Drinking water, freshly drawn from the mains supply.
 Contains the highest level of impurities
 Dissolved inorganic ions
 Dissolved and undissolved organic matter
 Dissolved gases (O 2, CO2)
 oxidation, PH change, incompatibility
 Microbially contaminated
 Not contain more than 0.1% total solids/residue/ (USP)
 Used in the early stages of cleaning pharmaceutical manufacturing
equipment, but, the final rinse is done by purified water

INTRODUCTION TO IPP-I 58
ii. Purified Water
 Prepared from potable water by:
Distillation

Reverse osmosis

demineralization (ion-exchange resins)

 Free of inorganic salts, organic matter and dissolved
gases

INTRODUCTION TO IPP-I 59
ii. Purified Water…
 Could contain:
 microorganisms.

 not more than 0.001% total solids/residues/. i.e 1mg /100 ml.

(0.001g/100ml)
 formulation of pharmaceutical dosage forms, except sterile
products

INTRODUCTION TO IPP-I 61
iii. Water for injection (WFI)
 Sterilized purified water
 stored in sterile, pyrogen free, tight containers
 Contain not more than 0.001% of total solids
 Uses
 formulation of sterile products
 cleaning of equipment and containers of sterile products

INTRODUCTION TO IPP-I 62
iv. Sterile water for injection
 WFI packed in single-dose containers of not more than 1lit
 Sterile and pyrogen free
 Don’t contain antimicrobial
 agent
Used as a solvent or diluent for already sterilized and packed
injectabe medications

INTRODUCTION TO IPP-I 63
Pharmaceutical water (summary)
Products Minimum acceptable quality of water
Vaccines (parentrals) WFI
Parentrals WFI
Dialysis Solutions WFI
Irrigation Solutions WFI
Nasal/Ear Preparations Purified water
Oral Preparations Purified water
Rectal/Vaginal Preparations Purified water

Water used during manufacture of medicinal products but not present in the final
formulation
Process Minimum acceptable quality of water
Granulation Purified water
Tablet coating Purified water

INTRODUCTION TO IPP-I 64
Non-aqueous vehicles
 Water couldn’t be used as a vehicle in some
cases
 Solubility problem
 Stability problem (hydrolysis)
 Sustained release product of a water soluble drug (oily injections)
 In such circumstances non-aqueous vehicles are used
 Alcohols
 Fixed oils
 Low [Link] PEGs

INTRODUCTION TO IPP-I 65
Ethanol
 Alcohol USP contains between 94.9 and 96.0% v/v ethyl alcohol

(ethanol)
 Widely used for external solutions; rarely used internally.
 commonly used as a co-solvent (e.g. hydroalcoholic solvents)
 Antimicrobial effect (>15%)
 Industrially methylated sprit (IMS)- used for external use.
 It is also useful for the extraction of crude drugs, being more
selective than water

INTRODUCTION TO IPP-I 66
Glycerol (Glycerin)
 Colourless, odourless, sweet viscous liquid
 It has similar co-solvency properties to ethanol.
 Used as a vehicle in some preparations.
 It is used as stabilizer and sweetener in internal preparations.
 In concentration above 20%v/v it acts as preservative

INTRODUCTION TO IPP-I 67
Propylene glycol
 an odourless, colourless, viscous liquid contain 2 hydroxyl groups

per molecule
 miscible with water, acetone, or chloroform in all proportions. But

not with oils

 As cosolvent with water for internal use
 Can be used alone for external use
 Is less viscous but better solvent than glycerin

INTRODUCTION TO IPP-I 68
Polyethylene glycol
 PEG is a polymer composed of repeating units of the monomer

ethylene oxide
 HO-CH2-(CH2-O-CH2-)n-CH2-OH

 available in a range of viscosity grades

 PEG 200, PEG 400 are preferred as
 co-solvents with alcohol or water

 formulation of water-miscible ointment bases

INTRODUCTION TO IPP-I 69
Fixed oils
 Vegetable origin, edible, digested in the gut
 Fatty acid esters of glycerol
 Almond oil, arachis oil, Corn oil, olive oil, caster oil, cottonseed oil,

soya been oil, etc.

 Used as a vehicle for lipophilic drugs: eg vitamins (A, D)
 Depot preparations of polar drugs (emulsion, suspension)
 Oily taste, hence unpleasant for oral use
 Encapsulated in soft gelatin capsules

INTRODUCTION TO IPP-I 70
Miscellaneous solvents
 Isopropyl myristate and isopropyl palmitate
 used as solvents for external use, particularly in cosmetics

 Dimethylformamide and dimethylacetamide

 used as solvents in veterinary formulation

 Xylene is present in some ear drops for human use to dissolve ear
wax

INTRODUCTION TO IPP-I 71
❷Preservatives
֍ Prevent microbial spoilage of the product
֍ minimize the risk of the consumer acquiring infection from DFs
֍ Ideally, preservatives should exhibit the following properties:
 possess a broad spectrum of antimicrobial activity

 chemically and physically stable over the shelf-life of product

 low toxicity & employed at low conc. than antiseptics

INTRODUCTION TO IPP-I 72
❷Preservatives…
Preservatives for oral solution
Benzoic acid and its salts (0.1–0.3%),
Sorbic acid and its salts (0.05–0.2%)
Alkyl esters of parahydroxybenzoic acid (0.001-0.2%)
 They are commonly called parabens

INTRODUCTION TO IPP-I 73
❷Preservatives…
Preservatives for topical solutions
 Chlorcresol,
 Chlorbutanol
 Parabens

INTRODUCTION TO IPP-I 74
❸Antioxidants
 Incorporated to enhance the stability by preventing chemical

degradation by oxidation
 Antioxidants commonly used for
Aqueous systems Oil systems
• Na Sulfite* • Ascorby palmitate
• Thioglycerol • Hydroquinone
l
• Na metabisulfite*
• Thiosorbitol • Propyl gallate
• Na bisulfite * • BHA
• Thiourea • BHT
• Ascorbic acid
• Thioglycolic acid • Tocophenols
• *Isoascorbic acid* • Lecithin
• Cysteire HCl
• Na thiosulfate*

INTRODUCTION TO IPP-I 75
❹Buffering Agents
 Enable the solution to resist any change in pH
 pH affects solubility, stability and safety
 Buffers usually contain mixtures of a weak acid & one of its salts (or

a weak base and one of its salts)

 Acetates (acetic acid & sodium acetate): 1–2%

 Citrates (citric acid & sodium citrate): 1–5%

 Phosphates (Na phosphate & di Na phosphate): 0.8–2%.

INTRODUCTION TO IPP-I 76
❺Viscosity enhancing agents
 Used
 in suspensions to deter sedimentation,
 in ophthalmic solutions to enhance contact time,
 to thicken topical creams, etc

 Non-ionic (neutral) polymers

 Cellulose derivatives, e.g.: MC, HEC, HPC
 Polyvinylpyrrolidone

 Ionic polymers
 sodium carboxymethylcellulose (anionic)
 Sodium alginate (anionic).

INTRODUCTION TO IPP-I 77
❻Isotonicity modifiers
Required for
 Solutions applied to mucus membranes,
 injections and
 ophthalmic solutions

Used to avoid irritation, pain, cell lysis

 E.g. NaCl and dextrose

INTRODUCTION TO IPP-I 78
❼Surface-active agents
 used to reduce surface or interfacial tension
 e.g. polysorbate 80, sodium lauryl sulfate, sorbitan monopalmitate
 Types of surface-active agents
(1) anionic
(2) cationic
(3) nonionic
(4) amphoteric

INTRODUCTION TO IPP-I 79
❽Emulsifying agent
 used to promote and maintain dispersion of finely divided particles

of a liquid in a vehicle
 e.g. acacia, cetyl alcohol, glyceryl monostearate, sorbitan

monostearate

INTRODUCTION TO IPP-I 80
❾Suspending agent
 used to reduce sedimentation rate of drug particles dispersed

throughout a vehicle
 e.g. hydroxymethyl cellulose, hydroxypropyl cellulose,

methylcellulose, tragacanth

INTRODUCTION TO IPP-I 81
10. Sweetening agents
 increase the palatability of the therapeutic agent.
 The main sweetening agents employed in oral preparations are
Sucrose, glucose

Polyhydric alcohols such as sorbitol, mannitol and, glycerol

Artificial sweeteners-saccharin sodium and aspartame.

INTRODUCTION TO IPP-I 82
Flavoring agents
 Objectionable taste in the formulation may lead to nausea, vomiting and
patient non-compliance.

 An attractive flavor will encourage palatability and easy administration.

INTRODUCTION TO IPP-I 83
11. Colouring Agents
 The Food Drug and Cosmetic Act of 1938 created three categories

of Dyes
 FD&C colors: These are colorants that are certifiable for use in

foods, drugs, and cosmetics.

 D&C colors: These are safe for use in drugs and cosmetics when
in contact with mucous membranes or when ingested.
 External D&C colors: These colorants, due to their oral toxicity,
are not certifiable for use in products intended for ingestion

INTRODUCTION TO IPP-I 84
Colouring Agents….
Widely used colorants in pharmaceuticals
 FD&C Blue No. 1 – Brilliant Blue, (blue shade)
 FD&C Blue No. 2 – Indigotine, (indigo
 shade)
FD&C Red No. 3 – Erythrosine, (pink
 shade)
FD&C Red No. 4 – Allura Red, (red
 shade)
FD&C Yellow No. 5 – Tartrazine, (yellow shade)
 FD&C Yellow No. 6 – Sunset Yellow, (orange shade)

INTRODUCTION TO IPP-I 85
Excipients for tablet preparation
Diluents or fillers
 used to increase the bulk (mass & volume) of the formulation

Binders:
 used to adhere the powdered drug & pharmaceutical ingredients

Disintegrants:
 used to promote tablet disintegration (break-up) in the gastrointestinal fluid

Lubricants:
 used to assist proper powder flow during manufacturing

INTRODUCTION TO IPP-I 86
Summary
 Physical Pharmacy
 Pharmaceutics
 Dosage forms
 Major consideration in DF design
 Route of Administration
 Pharmaceutical excipients
 Examples of excipients

INTRODUCTION TO IPP-I 87