Dosage Form Science
Contents:
1. Introduction to drug, dosage form
2. Need for Dosage Forms
3. Pre-formulation studies
4. Brief introduction of different dosage forms (DF)
Dosage Form Science:
o Pharmaceutics is the discipline of pharmacy that deals with the
process of turning a new chemical entity (NCE) or old drugs into
a dosage form to be used safely and effectively by patients. It is
also called the science of dosage form design.
o Drug is an agent intended for use in the diagnosis, mitigation,
treatment, cure or prevention of disease in man or other
animals.
o Dosage forms are the means (or the form) by which drug
molecules are delivered to sites of action within the body.
o Dosage form is a physical form of a pharmaceutical formulation
containing the drug and some inactive ingredients necessary to
make that particular physical form.
Need of Dosage Form:
o The potent nature and low dosage of most of the drugs make it difficult to
obtain the appropriate dose of a drug from the bulk material.
o Most of the drug substances are administered in milligram quantities, some
even in smaller amounts so, besides providing safe and convenient delivery
of accurate dosage, dosage forms are needed for additional reasons:
1. To protect the drug substance from the destructive influences of
atmospheric oxygen or humidity (coated tablets, sealed ampules).
2. To protect the drug substance from the destructive influence of gastric
acid after oral administration (enteric-coated tablets).
3. To conceal the bitter, salty, or offensive taste or odor of a drug substance
(capsules, coated tablets, flavored syrups).
4. To provide liquid preparations of substances that are either insoluble or
unstable in the desired vehicle (suspensions).
5. To provide clear liquid dosage forms of substances (syrups,
solutions).
6. To provide rate-controlled drug action (various controlled-release
tablets, capsules, and suspensions).
7. To provide optimal drug action from topical administration sites
(ointments, creams, transdermal patches, and ophthalmic, ear, and
nasal preparations).
8. To provide for insertion of a drug into one of the body’s orifices
(rectal or vaginal suppositories).
9. To provide for placement of drugs directly in the bloodstream or
body tissues (injections).
10. To provide for optimal drug action through inhalation therapy
(inhalants and inhalation aerosols).
11. To target the drug at desired site of action (e.g., nano-particulate
systems, liposomes).
ASA
Factors considered for selecting a Dosage Form:
1. The nature of illness (acute / chronic).
2. The manner in which it is generally treated.
3. Local effect or systemic effect.
4. Age (young and elderly patients).
5. Anticipated condition of the patient (pregnancy, lactation,
convulsions, comatosed etc.).
6. Identification of drug (color, size and shape).
Classification of Dosage Forms:
1-According to route of administration:
1-For systemic administration 2-For local administration
a. Peroral (p.o) a. Topical (on the skin or
mucosa)
b. Sublingual (S.L) and
buccal. b. Into/onto
c. Rectal – the eye, nose, ear
d. Parenteral – the oral cavity
e. Transdermal – the vagina, rectum
f. Inhalation – the skin
c. Oral (local effect within
GIT)
2-According to physical form:
1. Gaseous dosage forms
2. Liquid dosage forms
3. Semisolid dosage forms
4. Solid dosage forms
Pre-formulation Studies:
Preformulation is the process of optimizing a drug through the determination of its
physical and chemical properties considered important in the formulation of a stable,
effective, and safe dosage form.
The following pre-formulation studies are carried out to define the nature of the drug
substance.
1. Physical properties (physical description, particle size, amorphous / crystalline
structure, melting point, and solubility)
2. Chemical properties (chemical structure, form, and reactivity)
3. Biologic properties (its ability to get to a site of action and elicit a biologic response)
4. Microscopic Examination (particle size and size range along with the crystal structure)
5. Particle size (affect dissolution rate, bioavailability, content uniformity, taste, texture,
color, and stability, flow characteristics and sedimentation rate)
6. Polymorphism (different physicochemical properties of polymorphs, including melting
point and solubility)
7. Solubility especially aqueous system solubility for therapeutic efficacy.
Chemical modification of the drug into salt or ester forms is frequently
used to increase solubility.
8. Partition coefficient (measure of a molecule’s lipophilic character).
Important for extraction of crude drugs, extraction of drugs from
biologic fluids for therapeutic drug monitoring and affecting
absorption of drugs from dosage forms (ointments, suppositories,
transdermal patches).
9. Dissolution rate (the time it takes for the drug to dissolve in the fluids
at the absorption site), affecting drug absorption. The dissolution rate
of drugs may be increased by decreasing the drug’s particle size or by
incorporating highly water-soluble salt of the parent substance.
10. Membrane permeability (passage of drug molecules across biologic
membranes). The biologic membrane acts as a lipid barrier to most
drugs and permits the absorption of lipid-soluble substances by
passive diffusion, while lipid-insoluble substances can diffuse with
considerable difficulty.
11. Drug and drug product Stability (physical, chemical, biological etc.)
Components of dosage form:
o Pharmaceutical dosage form consists of :
1. Active ingredients
o These are the main components of a dosage form that produce
pharmacological effects on body when administered e.g., in a paracetamol
tablet, paracetamol (acetaminophen) is the active ingredient that has
analgesic and antipyretic properties.
2. Excipients
o These are pharmacologically inactive substances that act as carrier for drug
or adjuvants to facilitate the manufacturing process.
o Pharmaceutical excipients solubilize, suspend, thicken, dilute, emulsify,
stabilize, preserve, color, flavor, and fashion medicinal agents into
efficacious and appealing dosage forms.
Examples of excipients:
o Acidifying agents o Clarifying agents
o Alkalinizing agents o Emulsifying agents
o Adsorbents o Encapsulating agent
o Aerosol Propellant o Flavorant
o Air Displacement o Humectants
o Antifungal preservatives o Levigating agent
o Antimicrobial preservatives o Ointment base
o Antioxidants
o Plasticizer
o Buffering agents
o Solvent
o Chelating agents
o Colorants
o Stiffening agent
o Suppository base
o Surfactants o Tablet glidents
o Suspending agent o Tablet lubricants
o Sweetening agent o Tablet/ capsule opaquant
o Tablet polishing agent
o Tablet anti adherents
o Tonicity agent
o Tablet binders o Vehicle
o Tablet and capsule o Viscosity increasing agent
diluents
o Tablet coating agent
o Tablet disintegrant
Introduction to various dosage forms:
1-Powders:
o Powders are intimate mixtures of dry, finely divided
drugs or chemicals that may be intended for internal
or external use.
o Powders for internal use are known as oral powders
while those for external use are known as dusting
powders.
o The particles of pharmaceutical powders and
granules may range from being extremely coarse,
about 10 mm in diameter, to extremely fine, of 1 μm
or less.
o e.g., bacitracin zinc and polymyxin B sulfate dusting
powder is used as antiseptic and anti-infective.
2-Granules:
Granules are prepared agglomerates of small powder
particles. They are irregularly shaped but may be prepared to
be spherical.
o They are usually in the 4 to 12 mesh sieve size range.
o Granules can be compressed as tablets or can be filled in
capsule shells.
Effervescent granules contain a medicinal agent in a dry
mixture usually composed of sodium bicarbonate, citric acid,
and tartaric acid.
o When added to water, the acids and the base reacts to
liberate carbon dioxide, resulting in effervescence.
o The resulting carbonated solution masks undesirable taste
of medicinal agent and act as antacid.
o e.g., Sodium phosphate effervescent granules.
3-Tablets:
o Tablets are solid dosage forms containing medicinal agents, with or
without diluents.
o They may vary in size, shape, weight, hardness, thickness, and in other
aspects, depending on their intended use and method of manufacture.
o They are usually used orally but can also be given by other routes.
o e.g., Paracetamol tablets are used as analgesic and antipyretic.
4-Capsules:
o Capsules are solid dosage forms in which medicinal
agents and/or inert substances are enclosed in a small
shell of gelatin.
o Gelatin capsule shells may be hard (two piece)or soft
(one piece), depending on their composition.
o The two main types of capsules are:
1. Hard-shelled capsules, which are normally used for
dry, powdered ingredients.
2. Soft-shelled capsules, primarily used for oils and for
active ingredients that are dissolved or suspended in
oil.
o They vary in size from 000 (largest) to 5 (smallest).
o e.g., amoxicillin capsules.
5-Lozenges:
o These are solid dosage form of medicament meant for slow
dissolution in the mouth for treating cough.
o Lozenges are frequently called troches and sometimes
pastilles.
o e.g., liquorice lozenges are used for throat infections.
6-Suppositories:
o A suppository is a solid dosage form designed for easy insertion into
body orifices of rectum, vagina or urethra where it melts, soften or
dissolve to exert local or systemic effects.
o Vaginal suppositories are called pessaries while urethral suppositories
are called bougies.
o They have various shapes and weights depending on their use.
o e.g., Bisacodyl suppository is used to produce local cathartic effect.
7-Aerosols:
o Pharmaceutical aerosols are pressurized
dosage forms that upon actuation, emit a
fine dispersion of liquid and/or solid
materials containing one or more active
ingredients in a gaseous medium.
o Particles are less than 50 micrometer in
diameter.
o Aerosols can be used orally or topically to
dispense drugs to the site of action directly.
o e.g., Salbutamol aerosol.
8-Inhalations:
o Inhalations are liquid preparations
(solutions or suspensions) of volatile
substances administered by nasal or
oral respiratory route in the form of
vapor.
o Inhalations are used to relieve nasal
congestion and inflammation of
respiratory tract.
o They are added to hot water and
vapours are inhaled for 5 to 10 minutes.
o e.g., Menthol and Eucalyptus oil
inhalation is used as decongestant.
9-Sprays:
o Sprays are liquid preparations
(aqueous or oleaginous) in the form of
coarse droplets or finely divided solids
to be applied topically, usually to nasal
tract or to skin by a nebulizer.
o e.g., Atropine spray is used to treat
runny nose due to rhinitis.
10-Solutions:
o Solutions are “liquid preparations that
contain one or more chemical substances
dissolved in a suitable solvent or mixture of
mutually miscible solvents”.
o They may be used topically or orally.
o e.g., Aqueous iodine solution, potassium
permanganate topical solution as antiseptic
etc.
11-Syrups:
o Syrups are concentrated aqueous preparations
of a sugar or sugar substitute with or without
flavoring agents and medicinal substances.
o They may be medicated or non-medicated.
o e.g., Benadryl syrup used to cure cold due to
allergy.
12-Aromatic waters:
o Aromatic waters, also known as medicated waters, are
saturated solutions of aromatic or volatile substances in
water.
o Due to their pleasant odor, they are used as flavoring or
perfuming vehicles in certain pharmaceutical preparations.
o Sometimes, they exert mild therapeutic action.
o e.g., peppermint water and camphor water are used as
carminative.
13-Spirits:
o Solutions of aromatic materials are termed spirits if the
solvent is alcoholic e.g., peppermint spirit is used as
carminative and flavouring agent.
14-Elixirs:
o Elixirs are clear, sweetened hydro alcoholic solutions
intended for oral use and are usually flavored to enhance
their palatability.
o They can be medicated or non-medicated.
o Medicated elixirs have potent substances and non-
medicated elixirs are used as flavours or vehicles for other
liquid preparations.
o e.g., Phenobarbital Elixir is used to cure seizures and sleep
problems.
15-Tinctures:
o In medicine, a tincture is an alcoholic extract (e.g. of leaves or other
plant material) or solution of a non-volatile substance; e.g. of iodine,
mercurochrome).
o To qualify as a tincture, the alcoholic extract is to have an ethanol
percentage of at least 40-60%.
o They are prepared by maceration or percolation.
o e.g., compound benzoin tincture as antiseptic topically.
16-Emulsions:
o An emulsion may also be defined as a biphasic liquid
dosage form of medicament in which two immiscible
liquids (generally one of them is water and the other is
some lipid or oil) are made miscible by the addition of a
third substance known as emulgent or emulsifying
agent.
o They may be w/o or o/w type. w/o emulsion is used
topically while o/w emulsion is used orally.
o Injectable emulsions are also available.
o e.g., liquid paraffin emulsion, castor oil emulsion are
used as laxative.
17-Suspensions:
o Suspensions are biphasic liquid dosage form of medicament in which
finely divided solid particles ranging from 0.5-5.0 micron are suspended
or dispersed in a liquid or semi-solid vehicle.
o Suspensions can be used orally, topically or as injections depending on
their composition.
o e.g., ibuprofen oral suspension is used as antipyretic and analgesic.
18-Gargles:
o They are aqueous solutions used in the prevention or
treatment of throat infections.
o Usually they are prepared in a concentrated solution with
directions for the patient to dilute with warm water before
use.
o e.g., phenol gargles are used as antiseptic.
19-Mouthwashes:
o These are concentrated alcoholic or hydro alcoholic solutions
used for rinsing, deodorizing, cleansing, refreshing or
antiseptic action in mouth or buccal cavity.
o These are similar to gargles but are used for oral hygiene and
to treat infections of the mouth.
o e.g., compound sodium chloride mouthwash is used for bed
ridden patients for oral hygiene.
20-Infusions:
o These are dilute solutions containing the readily soluble
constituents of crude drugs and prepared by diluting 1 part
of concentrated infusion with 10 parts of water.
o e.g., concentrated compound gentian infusion is used to
treat wounds.
21-Linctuses:
o Linctuses are viscous, liquid oral preparations that are usually
prescribed for the relief of cough.
o They usually contain a high proportion of syrup and glycerol
which have a demulcent effect on the membranes of the
throat.
o e.g., codeine linctus is used for dry cough.
22-Liniments:
o Liniments are alcoholic or oleaginous solutions or emulsions of various
medicinal substances intended to be rubbed on the skin.
o Liniments with an alcoholic or hydroalcoholic vehicle are useful when
rubefacient, counterirritant, or penetrating action is desired; oleaginous
liniments are employed primarily when massage is desired.
o They should not be applied on broken skin.
o e.g., white liniment is used as rubefacient for sprains, sciatica and
rheumatic pains.
23-Collodions:
o Collodions are liquid preparations composed of pyroxylin dissolved in a
solvent mixture usually composed of alcohol and ether with or without
added medicinal substances.
o Collodions are intended for external use.
o When applied to the skin with a fine camel’s hair brush or glass applicator,
the solvent rapidly evaporates, leaving a filmy residue of pyroxylin.
o They are used for small cuts or abrasions and also used when prolonged
contact between skin and drug is required.
o e.g., salicylic acid collodion is used to remove warts.
24-Lotions:
o Lotions are emulsions or suspensions generally in an
aqueous vehicle, meant for external application to
the skin without friction.
o Lotions may be preferred over semisolid preparations
because of their non-greasy character and their
increased spreadability over large areas of skin.
o Lotions are thinner than creams. They absorb very
quickly and feel very light on the skin.
o e.g., calamine lotion is used for skin rash after small
pox and for eczema.
25-Paints:
o They are liquid preparations meant for external
application to the skin or mucous membrane. They
have a volatile solvent that evaporates leaving
behind a film of medicament.
o Throat paints are viscous preparations applied to
throat by a brush.
o e.g., compound iodine paint (Mandl’s paint) is used
for pharyngitis and tonsilitis.
26-Injections:
o Injections are sterile, pyrogen limited, liquid
preparations that contain one or more
medicaments dissolved or suspended in a
suitable vehicle and are intended to be
administered parenterally.
o Most injections go
1. into a vein (intravenous, IV),
2. into a muscle (intramuscular, IM),
3. into the skin (intradermal, intracutaneous), or
4. under the skin (subcutaneous, hypodermic).
o e.g., ampicillin injection used as antibiotic.
27-Eye drops:
o These are sterile, aqueous or oily solutions or suspensions for instillation into the
eye.
o These are applied into the space between eyeball and eye lids or onto the corneal
surface.
o Eye drops must be sterile, isotonic, buffered and free from foreign particles to avoid
irritation to eye.
o Eye drops have medicaments having antiseptic, anesthetic, anti-inflammatory,
mydriatic or miotic properties.
o e.g., Betnisole eye drops are used to treat inflammation of the eye.
28-Ear drops:
o These are liquid preparations in which the drug
is dissolved or suspended in a suitable vehicle
like water, alcohol or glycerin etc. and are
intended for instillation into the ear with a
dropper.
o They are used for cleansing of ear, wax softening
purpose or for treating ear infections.
o e.g., sodium bicarbonate ear drops are used to
soften wax.
29-Nasal drops:
o These are aqueous solutions intended
for instillation into the nostrils by a
dropper.
o They are used for analgesic or
vasoconstrictor properties.
o e.g., ephedrine nasal drops are used as
decongestant.
30-Enemas:
o Enemas are aqueous or oily solutions or suspensions intended for
introduction into the rectum for cleansing, therapeutic or diagnostic
purposes.
o Enemas are used for their purgative, sedative, anthelmintic, anti
inflammatory or nutritive effects e.g., olive oil enema.
o They may also be used for x-ray examination of lower bowel e.g.,
barium sulphate enema.
31-Creams:
o Pharmaceutical creams are semisolid preparations containing one or more
medicinal agents dissolved or dispersed either as W/O emulsion or O/W
emulsion or in another type of water-washable base.
o They have lighter body than ointments.
o Also because of water soluble base, they can be easily removed from skin and
clothing.
o Creams may be: Medicated for a specific action or Non-medicated as
emollient
o e.g., cetrimide cream is used for minor wounds, burns, cuts to prevent
infection.
32-Ointments:
o Ointments are semisolid preparations having fatty bases intended for
external application to the skin or mucous membranes.
o Ointments are immiscible, miscible or emulsifiable with the skin
secretion.
o They are used as emollient or protective agent
o Ointments may be medicated or not.
o e.g., compound benzoic acid ointment is used as fungicidal topically.
33-Pastes:
o Pastes are semisolid preparations intended for external application to
the skin.
o They generally contain a larger proportion of solid material (such as
25%) than ointments and therefore are stiffer and less penetrating.
o Because of the stiffness of pastes, they remain in place after
application and are effectively employed to absorb serous secretions.
o Pastes are usually employed for their protective action.
o e.g., zinc oxide paste is used as astringent for the treatment of eczema
and psoriasis.
34-Gels:
o Gels are defined as semisolid systems consisting of
dispersions made up of either small inorganic particles or
large organic molecules in an aqueous liquid vehicle
rendered jellylike by the addition of a gelling agent.
o Medicated gels may be prepared for administration by
various routes, including oral, the skin, the eye, the nose, the
vagina, and the rectum.
o e.g., milk of magnesia is used orally as antacid, dicloran gel is
used as analgesic topically.
35-Jellies:
o Jellies are a class of gels in which the structural coherent
matrix contains a high proportion of liquid, usually water.
o These are transparent or translucent non-greasy semi-solid
preparations meant for external application to the skin or
mucous membrane.
o e.g., Proflavin jelly is used as an antiseptic
36-Poultice:
o It is soft, viscous, pasty preparation
for external use. They are applied to
skin while they are hot.
o Poultice must retain heat for a
considerable time because they are
intended to supply warmth to
inflamed parts of body.
o e.g., Kaolin poultice (B.P.C.) is used
to alleviate pain by reducing
inflammation when applied to the
skin using gauze.
37-Plasters:
o Plasters are solid or semisolid adhesive masses spread on a
backing of paper, fabric, moleskin, or plastic.
o Plasters are applied to the skin to provide prolonged contact
at the site.
o e.g., salicylic acid plaster is used on the toes for removal of
corns.
References:
1. Ansel’s Pharmaceutical Dosage Forms And Drug Delivery Systems.
2. Pharmaceutics Basic Principles And Application To Pharmacy Practice
Edited By Alekha K. Dash, Somnath Singh And Justin Tolman.
3. Introduction To Pharmaceutics-ii (3rd Ed) By Ashok K. Gupta.
4. Pharmaceutical Dosage Forms And Drug Delivery (2nd Ed) By Ram I.
Mahato And Ajit [Link].