Notes on Different Dosage Forms

What is pharmaceutics?

• The discipline covering stages after drug discovery: isolation, purification, testing for efficacy and safety, and formulation into medicines.
• Simple definition: pharmaceutics converts a drug into a medicine.

Drug

• A substance intended for diagnosis, mitigation, treatment, cure or prevention of disease in humans or animals.
• Drugs are usually administered as formulated dosage forms rather than in crude form.

Dosage Forms

• Dosage forms are carriers that deliver the drug to action sites in the body.
• Each dosage form is a combination of the drug and excipients (non-drug additives).
• Excipients provide shaping, stability, palatability, and overall presentation.

Need For Dosage Forms

• Accurate dose $= d$ per administration.
• Protection: e.g., coated tablets, sealed ampoules.
• Protection from gastric juice: enteric-coated tablets.
• Mask unpleasant taste/odor.
• Deliver drugs within body tissues (e.g., injections).
• Sustained-release options.
• Facilitate insertion into body cavities (rectal, vaginal).
• Inhalation for optimum action; topical administration for local action (creams, ointments, emulsions, lotions).
• Use of vehicles for insoluble drugs.

Classification of dosage forms

• Solid dosage forms: tablets, capsules, pills, powders (internal/external), granules, etc.
• Liquid dosage forms: syrups, elixirs, linctuses, drops, liniments, lotions, gargles, mouth washes, sprays, eye/nasal drops, etc.
• Semi-solid dosage forms: suppositories, pessaries, ointments, creams, pastes, jellies.

Solid dosage forms

• Includes: Tablets, Pills, Capsules, Granules, Dusting Powders.
• Bulk solids: internal fine powders and granules; external dusting powders and insufflations; dentifrice; snuffs; etc.

Dusting Powders

• Applied externally to skin; must be very fine to avoid irritation. Sieve to $80$ to obtain fine powder.
• Made by mixing multiple ingredients; common inert carriers: talc or kaolin.
• Uses: antiseptic, astringent, absorbent, antiperspirant.
• Subtypes: I) Medical dusting powders; II) Surgical dusting powders.

Medical Dusting Powders

• Increase superficial skin condition.
• Not applied to wounds or burns.
• Must be free from dangerous pathogens.

Surgical Dusting Powders

• Used in body cavities and on major wounds/burns.
• Should be sterilized before use.
• Used for antiseptic/absorbent action.

Insufflations

• Medicated dusting powders introduced into body cavities (nose, throat, ear, vagina) via insufflator.
• Powder is sprayed as fine particles on site.
• Now available as pressure aerosols for potent drugs.
• Used for ENT infections to achieve local effect.

Snuffs

• Finely divided solid dosage forms inhaled into nostrils.
• Used for antiseptic, bronchodilator, and decongestant action.

Granules

• Granulation forms primary powders into larger particles to improve administration.
• Suitable for bitter/unpleasant powders that are not suitable as tablets/capsules or liquids due to bulk or stability.
• Prepared by mixing with excipients, granulating, drying, and sieving to desired size.
• Example: Effervescent granules.

Effervescent Granules

• For internal use; medicaments mixed with citric/tartaric acids and sodium bicarbonate; sweetening agents may be added.
• Upon dissolution in water, acid-base reaction yields effervescence.
• Prepared by two methods: I) Heat method; II) Wet method.

Heat method

• Use hot dish over boiling water bath; ensure rapid liberation of water of crystallization from citric acid; form coherent mass; sieve to size; dry at $60^{\,^ ext{o}}C$; package in airtight container.

Wet method

• Mix all ingredients; moisten with non-aqueous vehicle (e.g., alcohol) to form a coherent mass; sieve (no. $8$) to obtain granules; dry at $60^{\,^ ext{o}}C$; sieve again to break lumps; package airtight.

Tablets

• Solid dosage forms prepared by moulding or compression with or without excipients.
• Preparation methods: I) Dry granulation; II) Wet granulation.

Capsule

• Solid unit dosage forms with medicament(s) enclosed within a shell.
• Shell consists of two parts: Body and Cap.
• Generally prepared from gelatin.
• Gelatin types: I) Hard gelatin; II) Soft gelatin.

Pills

• Small rounded solid dosage forms for oral use; medicament mixed with excipients to form a firm plastic mass.
• Mass rolled into a uniform pill pipe and cut into uniform pills; coated for finish, taste, or stability.
• Nowadays largely outdated due to drawbacks such as disintegration variability and uniformity issues.

Liquid dosage forms

• Defined as solutions, suspensions, emulsions, and other liquid preparations for internal, external, or parenteral use.
• Solvent vs solute: the component present in large quantity is the solvent; the solute is the component in smaller quantity.
• Monophasic vs biphasic forms.

Aromatic Waters

• Medicated waters: clear, saturated aqueous solutions of volatile oils or aromatic substances.
• Used mainly as flavored/perfumed vehicles.
• Incompatibility issues can cause salting-out; care with storage.
• Preparation methods: Distillation (Rose water) or Solution process (Peppermint water).
• Distillation advantages: most satisfactory; disadvantages: slow/expensive; avoid direct heat to preserve aroma; distillate can be reprocessed.
• Solution process involves shaking volatile substance with purified water; may use talc as a filter aid.

Monophasic liquid dosage forms

• Represented by true or colloidal solutions; homogeneous systems; solvent is large-phase; solute is small-phase.
• Subclassified by use: I) Internal Use; II) External Use.

Monophasic liquid dosage forms for Internal Use

• Includes: Syrup, Elixirs, Linctuses, Drops.
• Also listed for external use: Liniments, Lotions, Gargles, Mouth Wash, Throat paints, Sprays, Inhalations, Nasal drops, Eye drops, Eye lotions, Ear drops.

Syrup

• Concentrated or saturated solution of sucrose in purified water; typical syrup is 66.7 ext{% w/w} sucrose.
• Medicated syrups contain active drugs; flavored syrups contain aromatic/flavored substances.

Importance of syrup

• Retards oxidation due to hydrolysis of reducing sugars present.
• High osmotic pressure helps prevent microbial growth.
• Palatable due to sweetness.

Elixirs

• Clear, sweetened hydroalcoholic preparations for oral use; medicated elixirs contain active drugs; non-medicated elixirs flavored.
• Composition: ethyl alcohol, water, glycerin/propylene glycol, coloring agent, flavor, preservative.

Linctuses

• Viscous liquid preparations for cough relief; contain demulcents, sedatives, and/or expectorants.
• Taken in small doses without dilution for prolonged effect.
• Simple syrup often used as vehicle; tolu syrup used for its aroma and mild expectorant action.

Drops

• Liquid preparations for oral administration; fat-soluble vitamins (e.g., A, D) in fish-liver oil may be in drop form.
• Precise dosing required; measuring tools include: $ext{accurately graduated dropper}$ or pre-calibrated dropper.

Monophasic liquid dosage forms for External use

• Liniments (external rub), Lotions (spread without friction), Gargles, Mouth washes, Throat paints, Sprays, Inhalations, Nasal drops, Eye drops, Eye lotions, Ear drops.

Liniments

• Liquid or semi-liquid for external skin application; usually alcoholic and oily (monophasic) or emulsified (biphasic).
• Alcoholic liniments provide rubefacient/counterirritant effects; penetrate skin better than oil-based liniments.
• Do not apply to bruised or broken skin.

Lotions

• Aqueous, alcoholic, or oily liquids for external use; applied without friction using absorbent material.
• Provide cooling, soothing, protective, and antiseptic action.

Gargles

• Aqueous solutions for throat infections; supplied concentrated with directions to dilute with warm water.
• Used for several seconds in contact with throat mucosa; antiseptic/antibiotic/anaesthetic actions.

Mouth wash

• Aqueous solutions for oral hygiene and infection treatment; contain antibacterial agents, alcohol, glycerin, sweeteners, flavoring, and coloring.

Throat paints

• Viscous liquids for mouth/throat infections; glycerin base provides adhesion and sweet taste.

Sprays

• Drug-containing media (aqueous, alcoholic, or glycerin) applied to throat/nose mucosa via atomizer.
• Nebulizers used to create very fine droplets for lung reach.

Inhalations

• Liquids with volatile substances to relieve congestion/inflammation of respiratory tract.
• Volatile components may require heating during use.

Nasal drops

• Solutions instilled into nose via dropper or squeeze bottle; local or systemic effects possible.
• Avoid oily nasal drops to prevent ciliary damage and potential lipoid pneumonia with long-term use.
• Isotonic and mildly buffered to pH $5.5-6.5$ for compatibility with nasal mucosa.

Eye drops

• Sterile, aqueous/oily solutions or suspensions for instillation into the eye.
• May contain buffers, stabilizers, surfactants, tonicity modifiers, etc.
• Single-dose containers should be preservative-free; multi-dose containers may include a dropper with a max volume of $10\,\text{mL}$.

Eye lotions

• Aqueous solutions for washing the eyes; supplied in concentrated form and diluted with warm water before use.
• Should be free of particulates; prepared fresh and not stored beyond about two days to prevent microbial growth.

Ear drops

• Solutions instilled into the ear to clean wax or treat mild infections.
• Bases include water, glycerin, propylene glycol, and dilute alcohol.

Enemas

• Rectal injections for evacuation, systemic absorption (retention), local effect, or radiographic examination.
• Retention microenemas are small-volume (~$30\,\text{mL}$).
• Starch enemas can be used as a vehicle for other medications.

Biphasic liquid dosage forms

• Consist of two phases: Emulsions (two liquid phases) or Suspensions (solid in liquid).

Emulsion

• Two immiscible liquids with a continuous phase and a dispersed phase; stabilized by an emulsifying agent.
• Globule size: $0.25-25\,\mu m$.
• Emulsions are thermodynamically unstable and tend to separate over time.
• Types: Simple (water-in-oil, $w/o$; oil-in-water, $o/w$); Microemulsions; Fine emulsions; Multiple emulsions (e.g., $w/o/w$, $o/w/o$).

Water in oil (w/o)

• Water dispersed; oil continuous; mainly for external use (lotions, creams).

Oil in water (o/w)

• Oil dispersed; water continuous; suitable for internal and external use (e.g., Vitamin A in oil, liquid paraffin in water).

Micro Emulsion

• Clear dispersions with very small globules (around $10\ \text{nm}$ or $0.01\ \,\mu m$); thermodynamically stable and optically transparent.

Fine emulsion

• Globule size around $0.25-25\,\mu m$; usually milky appearance.

Multiple emulsion

• Emulsion within an emulsion ($w/o/w$ or $o/w/o$); drugs in the innermost phase must cross two phase boundaries; used for sustained release or intramuscular therapy.

Identification tests for emulsions

• Dilution test, Conductivity test, Dye test, Fluorescence test, Cobalt chloride test, Filter paper test.

Dilution test

• If diluted with water and remains stable, it is likely $O/W$; if it breaks, likely $W/O$.

Conductivity test

• Conductivity indicates aqueous continuous phase ($O/W$); lack of conductivity indicates oil continuous phase ($W/O$).

Dye test

• Oil-soluble dye dispersed in emulsion; redistribution of color indicates continuous phase.

Fluorescence test

• Fluorescence under UV helps identify dispersed vs continuous phase.

Creaming test

• Direction of creaming indicates phase densities: water is denser than oil; water-in-oil emulsions tend to cream downward; oil-in-water emulsions cream upward.

Cobalt chloride test

• Emulsion on filter paper absorbed with cobalt chloride turns blue to pink; indicates $O/W$; may fail if unstable.

Filter paper test

• O/W spreads rapidly on filter paper; W/O migrates slowly; not suitable for highly viscous creams.

Suspensions

• Finely divided solid particles (roughly $0.5-5\,\mu m$) dispersed in a liquid or semisolid vehicle; external phases are typically aqueous for oral use; non-oral uses may be organic/oily.
• Particles act as dispersed phase; suspending agents provide stability.

Advantages of suspensions

• Improve chemical stability; can enhance bioavailability; allow controlled duration and onset of action; can mask taste.

Disadvantages of suspensions

• Physical stability issues (sedimentation, hard cakes); formulation challenges; need shaking; storage sensitivity to temperature changes.

Ideal qualities of a good suspension

• Settles slowly and re-disperses easily; pours readily; chemically inert; no hard cake; stable; masks taste.

Flocculated suspension

• Particles form loose networks (flocs) held by weak forces; easy to redisperse; better physical stability but lower bioavailability due to slower dissolution.

Deflocculated suspension

• Particles exist as discrete entities; strong repulsive forces prevent aggregation; slow sedimentation; difficult to redisperse and may form a hard cake; higher bioavailability but shorter shelf life.

Semisolid dosage forms

• External applications; include: ointment, creams, pastes, jellies, suppositories (unit dosage form).

Ointment

• Semisolid for skin/mucous membranes; medicament dissolved, suspended, or emulsified in base.
• No single ideal base; multiple bases are used.

Qualities of an ideal ointment base

• Inert, odorless, colorless, smooth; stable; compatible with skin and medicaments; spreads easily; does not retard wound healing; non-irritating.

Classification of ointment bases

• Oleaginous bases (hydrocarbons, vegetable oils, waxes)
• Absorption bases (anhydrous or water-absorbent; form w/o when mixed with water)
• Emulsion bases (o/w or w/o)
• Water-soluble bases (greaseless; typically polyethylene glycol polymers, carbowaxes)

Oleaginous bases

• Examples: soft paraffin, hard paraffin, liquid paraffin; may include vegetable oils.
• Pros: occlusive, prolonged skin contact; emollient.
• Cons: greasy; difficult to remove; poor drug absorption.

Absorption bases

• Absorb water to form w/o emulsions; two types: non-emulsified bases, and water-in-oil emulsions (e.g., lanolin).

Emulsion bases

• Can be o/w or w/o; easier to apply when o/w; w/o bases are greasier; commonly use emulsifying wax or agents to form emulsion.

Water soluble bases

• Greaseless ointment bases; primarily PEGs (carbowaxes); selection depends on molecular weight; non-volatile and inert.

Creams

• Viscous semisolid emulsions for external use; two types: I) Aqueous creams (o/w) – non-greasy; II) Oily creams (w/o) – greasier.
• Emulsifiers in aqueous creams can be anionic, cationic, or nonionic (e.g., polysorbates, triethanolamine soaps).
• Oily creams use emulsifying agents like wool fat, wool alcohols, beeswax, calcium soaps.
• Store in collapsible tubes; keep containers closed to prevent evaporation and contamination.

Pastes

• Thick, stiff semisolid external preparations; contain a high proportion of finely powdered medicaments; provide protective coating.
• Stored in non-absorbent or diffusion-resistant containers.

Jellies

• Transparent or translucent, non-greasy semi-solid for external use; also used to lubricate catheters, surgical gloves, rectal thermometers.
• Uses gelatin, starch, tragacanth, sodium alginate, cellulose derivatives.
• Types: Medicated jellies, lubricating jellies, miscellaneous jellies.

Suppositories

• Included in semisolid dosage forms; unit dosage form designed for insertion into body cavities (rectal, vaginal).

Summary concepts

• Pharmaceutics integrates drug science with practical formulation to ensure accurate dosing, stability, patient acceptability, and therapeutic efficacy.
• Dosage forms are tailored to route of administration, drug properties, and therapeutic goals.