EXAM STRATEGY & IMPORTANT QUESTIONS GUIDE

Ancient and Medieval Period:
During the Vedic era (around 3000 BC), the Atharva Veda and the classical compendia Charaka Samhita 🔊 and Sushruta Samhita 🔊 described more than 700 plant drugs and the methods used to prepare them. In the medieval period, the Unani system, brought to India by the Arabs and consolidated under the Mughals, introduced the hakim culture, in which pharmacy and medicine were practised by the same person. During the colonial era, the British East India Company imported European drugs and established apothecary shops in the major port cities.

Development of Pharmacy Education in India:
The first formal chemist-and-druggist shops in India were set up in Calcutta and Bombay around 1860. A structured Chemist & Druggist course was introduced at Madras Medical College in 1874. The modern degree-level pharmacy education began in 1932, when Professor M. L. Schroff started the B.Pharm course at Banaras Hindu University; he is therefore honoured as the "Father of Pharmacy Education in India". The D.Pharm course began in 1944. The Pharmacy Act was enacted in 1948, and under it the Pharmacy Council of India (PCI) was established in 1949; the Education Regulations followed in 1953. More recently, the Pharm.D programme of six years duration was introduced in 2008.

Pharmacy Industry and Professional Bodies:
The first fully Indian pharmaceutical company, Bengal Chemical & Pharmaceutical Works, was founded by Dr P. C. Ray in 1893. It was followed by Alembic Chemicals (1907), Cipla (1935), Ranbaxy (1961) and Sun Pharma (1983). The major professional bodies today are the Indian Pharmaceutical Association (IPA, 1939), the Indian Hospital Pharmacists Association (IHPA) and the Indian Pharmaceutical Congress Association (IPCA).

Pharmacy as a Career:
The D.Pharm (two years) leads to retail or hospital pharmacy practice, while the B.Pharm (four years) opens careers in industry, quality analysis, marketing and teaching. The Pharm.D (six years) prepares clinical pharmacists. A M.Pharm or Ph.D. leads to research and academia. Government openings include Drug Inspector, CDSCO and SDCO positions.

The Major Pharmacopoeias:
The four pharmacopoeias most important to Indian pharmacy practice are compared below.

Pharmacopoeia	Full form	Country	Publisher	First / Latest edition
IP	Indian Pharmacopoeia	India	IP Commission, Ghaziabad	1955 / IP 2022
BP	British Pharmacopoeia	United Kingdom	British Pharmacopoeia Commission, MHRA	1864 / BP 2024
USP-NF	United States Pharmacopeia – National Formulary	United States of America	USP Convention, Rockville	1820 / USP 46–NF 41
Extra Pharmacopoeia (Martindale)	The Complete Drug Reference	International reference	Pharmaceutical Press, UK	1883 / 40th edition

The Extra Pharmacopoeia (Martindale) is not a legally enforceable compendium; it is an international reference book containing exhaustive monographs of drugs, their indications and adverse effects worldwide.

Definition:
A dosage form is the pharmaceutical product containing the API together with suitable excipients, and it is designed to deliver an accurate and safe amount of drug to a specific site of action through a specific route of administration (for example, a tablet for the oral route, or an injection for the parenteral route).

Classification of Dosage Forms:
Dosage forms are classified in three principal ways.

A. Based on Physical State:
Solid forms include tablets, capsules, powders, granules, suppositories and lozenges.
Liquid forms include syrups, elixirs, solutions, suspensions, emulsions, drops and lotions.
Semisolid forms include ointments, creams, pastes, gels and jellies.
Gaseous forms include aerosols and inhalations.

B. Based on Route of Administration:
The oral route uses tablets, capsules and syrups; the topical route uses ointments, creams and lotions; the parenteral route uses intramuscular, intravenous and subcutaneous injections; the rectal route uses suppositories and enemas; the vaginal route uses pessaries and vaginal creams; the inhalation route uses aerosols and sprays; ophthalmic, nasal and otic routes use drops; and the transdermal route uses patches.

C. Based on Pattern of Drug Release:
Dosage forms may be conventional, sustained-release (SR), controlled-release (CR), delayed-release (DR) or targeted.

Definition:
A prescription is a written or electronic order issued by a RMP to a pharmacist, directing the supply of specified drugs to a particular patient together with appropriate dosing and administration instructions.

Parts of a Prescription (Six Parts):
(1) The date of issue, which also defines the validity of the prescription (usually 30 – 90 days for ordinary drugs, and 7 days for scheduled (narcotic) drugs).
(2) The superscription 🔊, represented by the symbol ℞ or Rx (from Latin recipe, meaning "take thou").
(3) The inscription, which is the main body of the prescription listing the drug name, strength, dosage form and quantity.
(4) The subscription, which contains directions to the pharmacist (for example "Mitte 30" meaning "dispense 30" or "m. ft. pulv." meaning "mix and make a powder").
(5) The signatura 🔊 or "Sig.", which conveys instructions directly to the patient (for example "1 tablet three times a day after food for 5 days").
(6) The renewal or refill instructions, along with the prescriber's signature, registration number, and the patient details (name, age, sex, and body weight).

Handling of a Prescription:
The following nine-step procedure should be followed when a prescription is received at the pharmacy.
(1) Receiving the prescription politely from the patient or carer and reading it carefully once.
(2) Reading and checking — verify the patient's details, the authenticity of the prescriber, the drug name, strength, quantity, the dose against standard therapeutic ranges, any possible interactions and known allergies.
(3) Numbering and dating the prescription for record purposes.
(4) Collecting and weighing the ingredients accurately.
(5) Compounding or dispensing the preparation strictly according to the formula.
(6) Labelling the container with the patient's name, drug name, dose, route, frequency, storage conditions, expiry date and pharmacy details.
(7) Packaging in a suitable container.
(8) Supply and counselling — explain the dose, timing, food instructions, possible side effects and proper storage.
(9) Record-keeping in the prescription register.

Common Errors in a Prescription:
Legibility errors arise from unclear handwriting. Omission errors occur when the strength, quantity, dosage form or route is missing. Commission errors refer to the wrong drug, wrong dose or wrong frequency being prescribed. Incompatibility errors arise when two drugs are chemically or therapeutically incompatible. Overdose or under-dose errors occur when the dose lies outside the therapeutic range. Abbreviation errors are due to ambiguous abbreviations (for example "U" mistaken for "0", or "qd" confused with "qid"). Duplication errors occur when drugs of the same class are prescribed twice.
The pharmacist's duty is to identify any such error, contact the prescriber, have it corrected, and only then dispense the medicine.

Definition:
Posology (from Greek posos = how much, logos = science) is the branch of pharmacology that deals with the dose or quantity of a drug to be administered to produce the desired pharmacological response.

Factors Affecting Dosage:
Dosage is influenced by a number of patient-related and drug-related factors.

Patient factors:
(1) Age: neonates require the smallest dose, followed by infants, children and adults, while the elderly often need a reduced dose because of decreased organ function.
(2) Body weight and body surface area determine the volume of distribution and therefore the dose.
(3) Sex: females, with a generally smaller body mass and a higher body-fat proportion, often require a lower dose.
(4) Pregnancy and lactation: dose must consider teratogenicity 🔊 and the passage of the drug into breast milk.
(5) Genetics or pharmacogenomics — for example, CYP2D6 polymorphism alters the dose of codeine and several antidepressants.
(6) Pathological conditions such as renal or hepatic impairment require dose reduction because clearance is decreased.
(7) Individual susceptibility — idiosyncrasy, allergy or acquired tolerance can demand dose adjustment.
(8) Circadian rhythm (chronopharmacology) — the same dose may act differently at different times of day.

Drug factors include the route of administration, the dosage form, the frequency of dosing, drug-drug and drug-food interactions, and environmental conditions (temperature and humidity during storage).

Paediatric Dose Calculation:
1. Based on Age.
Young's rule (for children aged 2 – 12 years): Child dose = Adult dose × [Age / (Age + 12)].
Dilling's rule (for children aged 4 – 18 years): Child dose = Adult dose × (Age / 20).
Fried's rule (for infants): Infant dose = Adult dose × (Age in months / 150).

2. Based on Body Weight.
Clark's rule: Child dose = Adult dose × (weight in lb / 150), or, equivalently, Adult dose × (weight in kg / 70).

3. Based on Body Surface Area (the most accurate method).
Child dose = Adult dose × (BSA of child / 1.73 m²).
The Mosteller formula is used for BSA: BSA (m²) = √[(height in cm × weight in kg) / 3600]. The average adult BSA is about 1.73 m².

4. Neonatal dose. Doses are usually calculated in mg per kg, with an adjustment for prematurity based on the post-conceptional age.

Weights and Measures:
Two systems of weights and measures are encountered in pharmacy.

Imperial (apothecaries') system:
For weight — 20 grains (gr) = 1 scruple, 3 scruples = 1 drachm, 8 drachms = 1 ounce, and 12 ounces = 1 pound (one grain ≈ 64.8 mg). For volume — 60 minims = 1 fluid drachm, 8 fluid drachms = 1 fluid ounce, 20 fluid ounces = 1 pint, and 8 pints = 1 gallon.

Metric (SI) system, which is the legal system in India since 1960. For weight, 1 g = 1000 mg = 10⁶ µg; for volume, 1 L = 1000 mL.

Useful conversions: 1 grain ≈ 64.8 mg; 1 fluid ounce ≈ 29.57 mL; 1 pint ≈ 473 mL; 1 gallon ≈ 3.785 L.

Percentage Solutions:
Three percentage expressions are used in pharmacy.
% w/w is the weight of solute (in grams) per 100 g of solution, used for solid-in-solid systems such as ointments.
% w/v is the weight of solute (in grams) per 100 mL of solution, used for solid-in-liquid systems and is by far the most common expression.
% v/v is the volume of solute (in millilitres) per 100 mL of solution, used for liquid-in-liquid systems such as ethanolic preparations.
Example: to prepare 500 mL of 2 % w/v potassium permanganate solution, weigh 2 × 5 = 10 g of KMnO₄ and dissolve it in water to make 500 mL.

Alligation Method:
Alligation is a quick arithmetic technique for mixing two solutions of different strengths to obtain a third of a required intermediate strength. The higher strength (H) is written in the top-left corner and the lower strength (L) in the bottom-left, with the required strength (R) in the middle. The parts of H needed equal (R − L), and the parts of L needed equal (H − R).
Example: to prepare 70 % alcohol from 90 % and 60 % stock solutions:
90 ── |70 − 60| = 10 parts of 90 %
       70
60 ── |90 − 70| = 20 parts of 60 %
Therefore the two stocks are mixed in the ratio 10 : 20, which simplifies to 1 : 2.

Proof Spirit:
In the United Kingdom, a proof spirit is defined as a spirit containing 57.06 % v/v of ethanol at 15.5 °C, which is said to be 100° proof. A spirit weaker than this is described as under-proof (UP), while a spirit stronger than proof is over-proof (OP). The proof strength of an under-proof sample is obtained as (100 − under-proof degrees), while the proof strength of an over-proof sample is (100 + over-proof degrees). Absolute ethanol therefore corresponds to 175.25° proof (or 75.25° OP).

Isotonic Solutions:
An isotonic solution exerts the same osmotic pressure as body fluids, approximately 310 mOsm/L; the reference preparations are 0.9 % sodium chloride, 5 % dextrose and Ringer's lactate. Four calculation methods are used to bring a pharmaceutical solution to isotonicity.
(1) The freezing-point method depends on the fact that body fluids depress the freezing point of water by 0.52 °C. The amount of adjusting substance (g per 100 mL) = (0.52 − a) / b, where a is the freezing-point depression produced by 1 % of the drug and b is the corresponding value for 1 % of the adjuster (for example, b = 0.576 for NaCl).
(2) The L-iso (molecular-weight) method uses the constant L_iso, whose value for NaCl is 3.4; the amount of drug giving isotonic effect = 0.52 × molecular weight / (i × L_iso).
(3) The sodium chloride equivalent (E) method defines E as the weight of sodium chloride producing the same osmotic effect as 1 g of the drug; the mass of NaCl to be added = 0.009 × V − (E × w).
(4) The White–Vincent method gives the volume of isotonic solution directly as V (mL) = W × E × 111.1, where W is the weight of drug in grams and E is its sodium-chloride equivalent.

Definition, Advantages and Disadvantages:
Powders are dry, finely divided preparations containing one or more drugs with or without excipients, intended for internal or external use.
Advantages: the dose can be flexibly individualised, the large surface area favours rapid absorption, powders are stable in dry form, and they are easy to administer to children or elderly patients who cannot swallow tablets.
Disadvantages: the bitter taste of the drug is not masked, powders are sensitive to atmospheric moisture, and they are not suitable for sustained-release preparations.

Classification of Powders:
Powders are classified in three ways.
(1) Based on composition, a simple powder contains a single drug, while a compound powder contains more than one drug.
(2) Based on dose, a bulk powder (for example an antacid) is self-measured by the patient, whereas a divided powder is supplied in individually measured doses in sachets or cachets.
(3) Based on route or intended use, powders may be oral, dusting (applied to skin), dentifrices (for teeth), insufflations (blown into body cavities) or snuffs (for nasal application).

Types of Powders in Detail:
Simple and compound powders are illustrated by the official Compound Powder of Rhubarb, which contains rhubarb, light magnesium oxide and ginger.
Dusting powders are free-flowing, sterile, finely subdivided powders applied directly to the skin; examples include Zinc Stearate Dusting Powder and Boric Acid Dusting Powder. They must be sufficiently fine to pass through a No. 80 to No. 100 sieve.
Effervescent powders and granules contain sodium bicarbonate together with an organic acid (citric or tartaric) and liberate carbon dioxide when added to water, giving a palatable preparation with rapid absorption; examples are ENO fruit salt and effervescent antacids.
Efflorescent powders contain hydrated salts that spontaneously lose their water of crystallisation on exposure to air and thereby become moist or sticky; examples include sodium carbonate, ferrous sulphate and citric acid. The problem is prevented by using the anhydrous salt or by storing the powder in tightly closed containers.
Hygroscopic powders absorb moisture from the atmosphere; examples include calcium chloride, zinc chloride and sodium bromide. They are protected by dispensing with a desiccant in a sealed container.
Eutectic mixtures form when two or more solid components are mixed in a particular ratio and the mixture liquefies at room temperature, because the melting point of the mixture is lower than that of any individual component. Typical examples are menthol + thymol, camphor + menthol, and aspirin + phenacetin. The problem is avoided either by dispensing the two components as separate powders or by adding an inert absorbent such as light magnesium oxide, light magnesium carbonate or kaolin to the mixture.

Geometric Dilution:
Geometric dilution is the standard technique for uniformly mixing a small amount of a potent drug with a large bulk of diluent. The smaller quantity (the potent drug) is first placed in the mortar; an equal quantity of diluent is then added and the mixture is triturated thoroughly. The quantity of diluent added is then doubled at each step and triturated again, and the process is continued until the whole of the diluent has been incorporated. For example, when 0.1 g of atropine is to be mixed with 9.9 g of lactose, the additions proceed as 0.2 g, 0.4 g, 0.8 g, 1.6 g, 3.2 g and 6.4 g. This prevents concentration gradients and ensures complete homogeneity of the final powder.

Advantages of Liquid Dosage Forms:
Liquid dosage forms are easy to swallow and therefore ideal for children, the elderly and patients with dysphagia 🔊. They permit flexible dosing, since the volume can be varied. Because the drug is already in solution, absorption is rapid and no disintegration step is needed. The drug is uniformly distributed, bitter taste and unpleasant odour can be masked with flavours and sweeteners, and formulations can be designed for site-specific use — ophthalmic, otic, nasal or topical.

Disadvantages of Liquid Dosage Forms:
Liquid preparations are chemically less stable than solids because the drug is susceptible to hydrolysis, microbial growth and oxidation in solution. They are bulky to store and transport. Incompatibilities are common, dosing is inaccurate when measured with household spoons, unpleasant taste is sometimes hard to mask completely, and the shelf-life is shorter than that of equivalent solid dosage forms.

Excipients Used in Liquid Dosage Forms:
Vehicles include water, alcohol, glycerol, propylene glycol, syrup and fixed oils.
Sweeteners include sucrose, saccharin, aspartame, stevia and sorbitol.
Flavours include orange, strawberry, peppermint and vanilla.
Colours are restricted to approved agents such as amaranth, erythrosine and tartrazine.
Preservatives include methyl paraben, propyl paraben, sodium benzoate, benzoic acid and chlorocresol.
Antioxidants include sodium metabisulphite, ascorbic acid, BHA and BHT.
Buffers such as citrate, phosphate and acetate maintain the pH.
Chelating agents such as EDTA sequester trace metal ions that would otherwise catalyse oxidation.
Viscosity enhancers include methylcellulose (MC), carboxymethylcellulose (CMC), tragacanth and acacia.

Solubility Enhancement Techniques:
(1) Particle size reduction through micronisation or nanosuspension increases the surface area exposed to the solvent.
(2) pH adjustment uses the fact that ionisation enhances the aqueous solubility of weak acids or bases.
(3) Cosolvency 🔊 uses the addition of water-miscible solvents such as ethanol, glycerol or polyethylene glycol.
(4) Hydrotropy 🔊 uses high concentrations of a hydrotrope such as sodium benzoate, urea or sodium citrate.
(5) Surfactants or micellar solubilisation using agents such as polysorbate 80 (Tween 80), Span and SLS.
(6) Complexation, particularly as inclusion complexes with cyclodextrins such as β-CD or hydroxypropyl-β-CD.
(7) Salt formation, by converting a weak acid to its sodium or potassium salt.
(8) Solid dispersions with hydrophilic polymers such as PEG or PVP.
(9) Prodrug approach — formulating a more soluble prodrug that is converted in vivo to the active drug.
(10) Use of a more soluble polymorph or the amorphous form of the drug.

Definitions and Key Features:
The nine most important monophasic preparations are compared in the table below.

Preparation	Route / Site	Key feature	Example
Gargles	Throat (head tilted back; not swallowed)	Supplied concentrated; diluted before use	Iodine gargle; Potassium chlorate gargle
Mouthwashes	Oral cavity	Ready-to-use antiseptic or deodorant	Chlorhexidine; povidone-iodine
Throat paints	Throat (applied with a brush)	Viscous; glycerine or honey base	Mandle's Paint (I₂ + KI + glycerin)
Ear drops	External auditory canal	Viscous (glycerin or oil); warmed to body temperature	Chloramphenicol, clotrimazole ear drops
Nasal drops / sprays	Nasal cavity	Isotonic; pH 5.5 – 7.5	Xylometazoline, saline drops
Enemas	Rectum	Evacuant, retention, diagnostic or nutrient	Soap enema, glycerin enema, barium enema
Syrups	Oral	Aqueous solutions of sucrose (≥ 66.7 % w/w) ± drug + flavour	Simple Syrup IP; cough syrups
Elixirs	Oral	Clear, sweetened, hydroalcoholic (8 – 40 % ethanol)	Paracetamol elixir, piperazine elixir
Liniments	Topical (WITH friction)	Alcoholic or oily; NEVER on broken skin	Turpentine liniment, methyl salicylate liniment
Lotions	Topical (WITHOUT friction)	Aqueous; may contain alcohol + glycerin; cooling	Calamine lotion, White lotion

Representative Preparations:
Simple Syrup IP is prepared by dissolving 66.7 g of sucrose in sufficient distilled water to produce 100 mL, applying gentle heat and then filtering. It has a density of about 1.32 g/mL and a refractive index of 1.445.
Iodine Gargle BPC contains 2.5 % iodine solution along with alcohol and water and is diluted 1 : 30 with warm water before use.
Calamine Lotion BP contains 15 % calamine, 5 % zinc oxide, bentonite magma, glycerol and calcium hydroxide solution; it is a shaking lotion that gives a cooling, astringent effect.
Turpentine Liniment BP contains 7.5 % soft soap, 5 % camphor, 65 % turpentine oil and water, and is used as a counter-irritant.

Classification:
Suspensions are classified according to route and to the state of flocculation.
Based on route of administration: oral (antacids and antibiotics), topical (calamine), ophthalmic (hydrocortisone) and parenteral (procaine penicillin, insulin zinc).
Based on physical system: flocculated and deflocculated.

Flocculated versus Deflocculated Suspensions:

Feature	Flocculated	Deflocculated
Particles	Form loose aggregates (flocs)	Exist as separate entities
Rate of settling	Fast	Slow
Sediment volume	Large, loose and fluffy	Small and compact
Supernatant	Clear	Cloudy
Cake formation	No cake; easy redispersion	Hard cake forms; difficult to redisperse
Appearance	Less elegant	More elegant initially
Pharmaceutical preference	Preferred (redisperses easily)	Not preferred for medicinal use

Methods of Preparation:
Two principal methods are used.
(1) In the dispersion method, the powdered drug is first triturated with a wetting agent such as glycerol, alcohol or propylene glycol, which reduces surface tension and displaces air from the particle surface; the wetted drug is then dispersed in the vehicle containing a suitable suspending agent.
(2) In the precipitation method, the drug is first dissolved in a non-solvent and then added to the vehicle, in which very fine particles precipitate out. This has three sub-types — organic solvent precipitation (drug in alcohol or propylene glycol added to water), pH-change precipitation (where a shift of pH alters ionisation and causes precipitation), and double decomposition, in which two soluble reactants give an insoluble product.

Suspending and Flocculating Agents:
Suspending agents act as viscosity enhancers and may be natural (acacia, tragacanth, sodium alginate, bentonite 🔊, carbomer), semi-synthetic (CMC, MC, HPMC) or synthetic (Carbopol, polyvinyl alcohol).
Flocculating agents produce controlled flocculation; they include electrolytes (NaCl, KCl, citrate), small amounts of surfactants, and polymers such as starch and alginates.

Stability Problems and Their Solutions:
(1) Sedimentation follows Stokes' law 🔊 v = 2 r² (ρ_s − ρ_l) g / 9 η; it is reduced by decreasing particle size, increasing the viscosity of the vehicle and minimising the density difference between solid and liquid.
(2) Caking is prevented by controlled flocculation.
(3) Crystal growth (Ostwald ripening) is prevented by using a single stable polymorph and by adding a protective colloid.
(4) Particle-size change and polymorphic transition are minimised by formulating with the thermodynamically stable polymorph and a viscosity enhancer.
(5) Microbial contamination is prevented by incorporating a suitable preservative (for example parabens).

Classification of Emulsions:
Emulsions are classified by type and by droplet size.

By type:
An O/W emulsion has oil droplets dispersed in a continuous water phase; it feels non-greasy and is easily washable (for example milk, calamine O/W lotion and most oral emulsions).
A W/O emulsion has water droplets dispersed in a continuous oil phase; it feels greasy and is occlusive (for example butter, cold cream and zinc cream).
Multiple emulsions (W/O/W or O/W/O) are emulsions within an emulsion and are used for sustained drug release.

By droplet size: macroemulsions (greater than 1 µm) are opaque, while microemulsions (10 – 100 nm) are transparent and thermodynamically stable.

Emulsifying Agents:
Emulsifying agents are classified by origin and by HLB value.
Natural emulsifiers include acacia, tragacanth, agar, lecithin, egg yolk, cholesterol, beeswax and wool fat.
Semi-synthetic emulsifiers include MC, CMC and carbomers.
Synthetic emulsifiers are classified further as anionic, cationic or non-ionic. Anionic examples include sodium and potassium soaps and sodium lauryl sulphate (produce O/W emulsions). Cationic examples include cetrimide and benzalkonium chloride (O/W and antimicrobial). Non-ionic examples include Spans (low HLB; W/O) and Tweens (high HLB; O/W), which are the most stable and most widely used.
On the HLB scale, a value of 3 – 6 indicates a W/O emulsifier, 8 – 18 an O/W emulsifier, and 13 – 15 a detergent.

Identification Tests for Emulsion Type:
(1) Dilution test — an O/W emulsion dilutes readily in water, while a W/O emulsion dilutes in oil.
(2) Dye test — a water-soluble dye such as amaranth colours an O/W emulsion uniformly, whereas an oil-soluble dye such as Sudan III 🔊 colours a W/O emulsion uniformly.
(3) Conductivity test — an O/W emulsion conducts electricity, while a W/O emulsion does not (the bulb of a conductivity apparatus remains dark).
(4) Fluorescence test — oils fluoresce under ultraviolet light; a W/O emulsion fluoresces continuously, while an O/W emulsion shows only spots of fluorescence.
(5) Cobalt chloride paper test — filter paper impregnated with anhydrous CoCl₂ (blue) turns pink only when wetted with an O/W emulsion.

Methods of Preparation:
(1) Continental (Dry-Gum, 4 : 2 : 1) method: the gum (acacia) is first triturated with the oil, and the water is then added all at once in the ratio oil : water : gum = 4 : 2 : 1. A soft clicking sound during trituration indicates formation of the primary emulsion.
(2) English (Wet-Gum) method: the gum is triturated with water first to form a mucilage, and the oil is then added gradually in portions. This method is more time-consuming but gives a finer emulsion.
(3) Bottle (Forbes) method: used for volatile oils; the oil, gum and water are shaken together in a strong bottle.
(4) Beaker / Phase-Inversion-Temperature (PIT) method: used at industrial scale.
(5) Auxiliary method: a small amount of an auxiliary emulsifier such as alcohol or glycerol is added to aid emulsification.

Stability Problems of Emulsions:
(1) Creaming is a reversible gravitational separation in which the cream rises in O/W emulsions or the oil sinks in W/O emulsions. It is reduced by increasing the viscosity of the continuous phase and reducing the droplet size (Stokes' law).
(2) Cracking 🔊 is the complete, irreversible coalescence of droplets into two distinct layers. It is caused by addition of electrolytes, use of incompatible emulsifiers, extreme temperatures or microbial growth.
(3) Phase inversion is the conversion of an O/W emulsion to W/O (or the reverse), caused by temperature change, addition of a soluble salt or a large alteration in the oil-water ratio.
(4) Microbial growth is prevented by incorporating a suitable preservative.
(5) Ostwald ripening — small droplets dissolve in the continuous phase and redeposit on larger droplets, gradually increasing the mean droplet size.

Definition and Types:
Suppositories are solid unit preparations inserted into body cavities, where they melt, dissolve or soften at body temperature and release the drug for local or systemic action.
The four common types are as follows.
Rectal suppositories are bullet- or torpedo-shaped and weigh 1 – 3 g in adults and about 1 g in infants.
Vaginal suppositories (pessaries 🔊) are cone- or pear-shaped and weigh 2 – 5 g.
Urethral suppositories (bougies 🔊) are pencil-shaped and weigh about 4 g in males and 2 g in females.
Nasal and ear suppositories (nasules and aurisoria) are rarely used now.

Advantages and Disadvantages:
The chief advantages are that the suppository bypasses first-pass metabolism of the liver, is useful when the patient is vomiting, unconscious or an infant, can give a local effect (for example in haemorrhoids), and often gives faster onset than the oral route.
The main disadvantages are temperature-sensitive storage, patient inconvenience, variable absorption, and sometimes poor patient acceptance.

Suppository Bases:
A. Fatty bases melt at body temperature (30 – 36 °C).
Theobroma oil 🔊 (cocoa butter) is the classical natural base; it melts at 30 – 36 °C but exhibits polymorphism (α, β, β′ and γ forms).
Witepsol, Suppocire and Massa Estarinum are modern synthetic hard fats that show no polymorphism and do not require mould lubrication.

B. Water-soluble / water-miscible bases dissolve in body fluids rather than melt.
A glycero-gelatin base contains glycerol 70 %, gelatin 20 % and water 10 %; it is used mainly for vaginal suppositories.
Polyethylene glycol (PEG / Macrogol) bases are mixtures of PEG 1000, 4000 and 6000; they are stable at room temperature and do not require refrigeration.

C. Emulsion bases are blends of fatty and water-miscible materials.

Methods of Preparation:
(1) Hand rolling or moulding is an old and now obsolete method.
(2) Fusion (pouring) method — the base is melted, the drug mixed in, the mixture poured into a lubricated mould, cooled, trimmed and packed. The lubricant is arachis oil or soft paraffin for theobroma-oil suppositories, and soap spirit for PEG-based suppositories.
(3) Compression method uses cold compression of a triturated drug-base mass, making it suitable for heat-sensitive drugs.
(4) Injection moulding is used industrially to produce polythene-shell suppositories.

Displacement Value (DV):
The displacement value is defined as the number of grams of a drug that displaces 1 g of the suppository base from a standard mould. It is needed because different drugs have different densities, so that the same volume does not correspond to the same weight. Typical pharmacopoeial displacement values are: bismuth subgallate 2.7, zinc oxide 4.7, aspirin 1.1, boric acid 1.5, morphine HCl 1.6, pethidine 1.6, phenobarbital 1.1, paracetamol 1.5 and hamamelis extract 1.5.
Formula: Weight of base required = Mould capacity − (Weight of drug / DV).
Worked example: to prepare 10 suppositories, each of 2 g, containing 100 mg of zinc oxide (DV = 4.7): the total drug is 1 g, the total mould capacity is 20 g, and the base required = 20 − (1 / 4.7) = 20 − 0.213 = 19.79 g.

Evaluation Tests:
(1) Weight variation (uniformity of mass): twenty suppositories are weighed and the mean individual weight must be within ± 5 % of the stated weight.
(2) Melting-point or softening-point test: the suppository must melt at body temperature.
(3) Liquefaction or disintegration time: less than 30 minutes for fatty bases and less than 60 minutes for water-soluble bases.
(4) Content uniformity: the drug is assayed in individual suppositories.
(5) Dissolution test using a modified USP basket or paddle apparatus.
(6) Hardness (crushing strength).
(7) Microbial limit test.

Definition:
A pharmaceutical incompatibility is an undesirable physical, chemical or therapeutic change that occurs when two or more ingredients in a prescription are combined, leading to loss of potency, development of toxicity, or an unacceptable change in appearance.

1. Physical Incompatibility:
A physical incompatibility involves a change in the physical state without any chemical reaction. The common types are described below.
Insolubility occurs when a large quantity of an insoluble substance is added to the vehicle; it is corrected by increasing the volume of vehicle, wetting with glycerol, or adding a suspending agent.
Immiscibility, as with oil and water, is corrected by adding an emulsifier.
Liquefaction / eutectic mixtures — for example, menthol with camphor — is corrected by adding an inert absorbent such as light MgO or kaolin.
Precipitation — the addition of water to an alcoholic tincture causes resin to precipitate; it is corrected by diluting slowly and adding a protective colloid.
Adsorption refers to the loss of drug on to container surfaces or filters.

2. Chemical Incompatibility:
A chemical incompatibility involves a chemical reaction that alters the identity or potency of the drug. The main types and their examples are as follows.
(a) Oxidation / reduction — for example, ascorbic acid is readily oxidised by atmospheric oxygen.
(b) Hydrolysis — esters such as aspirin and procaine, and the β-lactams such as penicillins, undergo hydrolysis in aqueous solution.
(c) Racemisation 🔊, which reduces the activity of the drug.
(d) Salt formation / precipitation — alkaloidal salts are precipitated by alkalies, and tannic acid precipitates alkaloids.
(e) Decomposition with gas liberation — sodium bicarbonate with an acid liberates CO₂.
(f) Complexation — tetracycline combines with Ca²⁺ or Fe²⁺ to give an insoluble chelate.
(g) Atmospheric oxidation — drugs such as adrenaline darken on exposure to air.
Typical prescriptions that pose chemical problems include an alkaloidal salt with an alkali carbonate (free base precipitates; corrected by reducing the alkali or using a syrup vehicle), tannin-containing tinctures with alkaloidal salts (tannate precipitates; use compound tragacanth powder), iodine with starch (deep-blue complex), and calomel with potassium iodide (liberates free iodine, which is toxic).

3. Therapeutic Incompatibility:
A therapeutic incompatibility arises when two or more drugs with antagonistic, additive or potentiating actions are prescribed together, reducing the therapeutic effect or increasing toxicity.
Examples include antagonism (prescribing a sedative along with a stimulant), additive action or synergism (two CNS depressants such as a benzodiazepine with alcohol, producing excessive sedation), overdosing (two preparations that both contain paracetamol), duplication (two antibiotics of the same class) and drug–food interactions (tetracycline taken with milk, which is rich in Ca²⁺).
The pharmacist's role is to identify such incompatibilities, query the prescriber, suggest a substitute, and counsel the patient.

Classification:
Semisolid preparations are classified as follows.
Ointments are oily or greasy preparations based on hydrocarbon, absorption, W/O, O/W or water-soluble bases.
Creams are semisolid emulsions, either O/W (vanishing cream) or W/O (cold cream).
Pastes contain more than 25 % of finely dispersed solids and are therefore stiffer than ointments.
Gels and jellies are transparent semisolids based on a hydrophilic polymer.
Other semisolid forms include semisolid liniments, plasters and poultices.

Types of Ointment Bases:
Ointment bases are conventionally grouped into four categories as summarised below.

Type of base	Composition	Property	Example
Hydrocarbon (oleaginous)	Petroleum derivatives	Occlusive; insoluble in water	Soft paraffin, white paraffin, hard paraffin
Absorption	Oleaginous base plus W/O emulsifier	Can absorb water	Wool fat, wool alcohols
Water-removable (O/W emulsion)	O/W emulsion	Washable and non-greasy	Hydrophilic ointment, vanishing cream
Water-soluble	PEG mixtures	Greaseless; washable	PEG 4000 + PEG 400

Methods of Preparation:
(1) Fusion method — the high-melting-point components of the base are melted together first (melting the highest-melting component first), the lower-melting components are added, the mixture is stirred continuously during cooling, and the drug is incorporated when the mass is close to congealing. This method is used mainly for ointments.
(2) Trituration / incorporation method — the drug is triturated with a small portion of the base in a mortar using the principle of geometric dilution; solid drugs are first levigated 🔊 with a small amount of liquid such as water or mineral oil.
(3) Emulsification method — the aqueous and oily phases are heated separately to about 70 °C and combined with continuous stirring until cool; this is the method of choice for creams.
(4) Mechanical method — industrial preparation using roller mills or colloid mills.

Excipients in Semisolid Dosage Forms:
The common excipients are the base itself, emulsifiers, humectants (glycerol, propylene glycol), preservatives (methyl and propyl parabens), antioxidants (BHT, tocopherol), penetration enhancers (DMSO, urea, surfactants), buffers, pH adjusters and perfumes.

Evaluation of Semisolid Dosage Forms:
(1) Appearance and homogeneity.
(2) pH, which should be close to that of skin (5.0 – 6.5).
(3) Viscosity and rheology, usually measured with a Brookfield viscometer; a pseudoplastic flow is generally desired.
(4) Spreadability, assessed by placing the sample between two glass slides with a fixed weight and measuring the area covered.
(5) Extrudability, the ease with which the product flows from the tube.
(6) Drug content assay.
(7) In-vitro drug release or diffusion, usually performed in a Franz diffusion cell.
(8) Stability — accelerated and real-time studies, including checking for phase separation.
(9) Microbial limits test.
(10) Skin irritation / allergy assessed by the Draize test.

Routes (Mechanisms) of Penetration:
Three pathways are recognised by which a drug can cross the stratum corneum.
(1) The transepidermal (transcellular) route takes the drug directly through the corneocytes and their surrounding lipid matrix; this is the main route for most drugs.
(2) The intercellular (paracellular) route carries the drug around the corneocytes through the lipid matrix; this is the principal route for lipophilic drugs.
(3) The transappendageal route carries the drug through the hair follicles, sebaceous glands and sweat glands; although quantitatively minor, it is significant for small ions and polar drugs.

Factors Influencing Penetration:
A. Drug factors. The molecular weight should preferably be less than 500 Da; the lipophilicity (log P) should lie between 1 and 3; a higher concentration increases flux according to Fick's first law 🔊 (J = D × ΔC / h); and the un-ionised form of the drug penetrates better than the ionised form. Particle size and solubility also matter.

B. Vehicle / formulation factors. The type of base (lipophilic versus hydrophilic) determines partition. Penetration enhancers (DMSO, urea, propylene glycol, azone and certain surfactants) reversibly alter skin permeability. The pH of the formulation affects drug ionisation, and occlusion of the skin increases hydration and thus permeability.

C. Skin factors. The thickness of the stratum corneum varies regionally (palm and sole thick, eyelid thin). Hydration increases permeability. Both neonatal and elderly skin are thinner. Increased blood flow (for example after massaging) increases clearance from the dermis. Diseased skin (eczema, burns) shows increased penetration. Body-site order is typically scrotum > face > forearm > palm.

D. Environmental factors. Higher temperature and humidity both increase penetration.

Given Data:
Number of suppositories to dispense = 12; an extra one is prepared, so the total = 13.
Weight of each suppository = 2 g.
Aspirin per suppository = 0.2 g.
Displacement value of aspirin = 1.1.

Calculation:
Total mould capacity = 13 × 2 g = 26 g.
Total aspirin required = 13 × 0.2 g = 2.6 g.
Weight of base displaced by aspirin = 2.6 / 1.1 = 2.36 g.
Weight of theobroma oil required = 26 − 2.36 = 23.64 g.

Answer:
The pharmacist should weigh 2.6 g of aspirin and 23.64 g of theobroma oil. Prepare 13 suppositories and dispense 12, keeping one as an excess to allow for trimming losses.

Principle:
The alligation method is based on the principle that, when two solutions of different strength are mixed, the amount of solute gained by the weaker solution multiplied by its parts must equal the amount lost by the stronger solution multiplied by its parts. The two simple rules are: Parts of stronger = (Required − Weaker) and Parts of weaker = (Stronger − Required).

Arrangement of Values:
The usual cross-wise arrangement is shown in the table below.

Stronger (H)	Required (R)	Parts of stronger = R − L
—	Mean value	—
Weaker (L)		Parts of weaker = H − R

Worked Example:
Prepare 500 mL of 40 % alcohol from 90 % and 20 % stock solutions.
Parts of 90 % stock = |40 − 20| = 20 parts.
Parts of 20 % stock = |90 − 40| = 50 parts.
Total parts = 20 + 50 = 70.
Volume of the 90 % stock required = 500 × (20 / 70) = 142.86 mL.
Volume of the 20 % stock required = 500 × (50 / 70) = 357.14 mL.