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Pharmacy Board Exam45 min read
Pharmaceutics
Dosage Forms, Drug Formulation & Delivery Systems
In This Section
1. Introduction to Pharmaceutics
Definition & Scope
Pharmaceutics is the science of converting active pharmaceutical ingredients (APIs) into safe, effective, and stable dosage forms suitable for patient use.
Key Objectives
- • Optimize drug delivery to target site
- • Ensure accurate and reproducible dosing
- • Maintain drug stability during storage
- • Improve patient acceptability and compliance
Sub-disciplines
- • Biopharmaceutics
- • Pharmacokinetics
- • Physical pharmacy
- • Industrial pharmacy
Preformulation Studies
Investigation of physical and chemical properties of a drug substance alone and combined with excipients.
Physical Properties
- • Particle size & shape
- • Crystallinity
- • Polymorphism
- • Melting point
Chemical Properties
- • pKa value
- • Solubility (aqueous/lipid)
- • Stability (pH, temp, light)
- • Partition coefficient
Powder Properties
- • Bulk/tapped density
- • Flowability
- • Compressibility
- • Hygroscopicity
Excipients Classification
| Category | Function | Examples |
|---|---|---|
| Diluents/Fillers | Add bulk to reach workable tablet size | Lactose, MCC, starch, mannitol |
| Binders | Hold powder particles together | PVP, HPMC, starch paste, gelatin |
| Disintegrants | Aid tablet breakup in GI tract | CCS, SSG, crospovidone |
| Lubricants | Reduce friction during compression | Magnesium stearate, stearic acid |
| Glidants | Improve powder flow | Colloidal silica, talc |
| Preservatives | Prevent microbial growth | Parabens, benzalkonium chloride |
2. Solid Dosage Forms
Tablets
Solid dosage forms containing API with or without excipients, made by compression or molding.
Manufacturing Methods
Direct Compression
- • No granulation needed
- • Blend → Compress
- • Requires good flow
- • Heat-sensitive drugs
Wet Granulation
- • Binder solution added
- • Improves flow & compressibility
- • Requires drying step
- • Most common method
Dry Granulation
- • Roller compaction/slugging
- • No water/heat
- • Moisture-sensitive drugs
- • High-dose drugs
Types of Tablets
Immediate Release
- • Conventional tablets - disintegrate quickly
- • Chewable tablets - masticated before swallowing
- • Orally disintegrating (ODT) - dissolve in mouth
- • Effervescent - CO₂ release in water
Modified Release
- • Extended-release (ER) - prolonged action
- • Delayed-release - enteric coated
- • Controlled-release - constant rate
- • Pulsatile - timed intervals
Tablet Defects
Capping: Top separates as a cap (entrapped air, low moisture)
Lamination: Horizontal splitting into layers
Sticking/Picking: Material adheres to punch (excess moisture)
Weight variation: Inconsistent die filling (poor flow)
Capsules
Hard Gelatin Capsules
- Composition: Gelatin, water, plasticizers, colorants
- Contents: Powders, pellets, granules, small tablets
- Sizes: 000 (largest) to 5 (smallest)
- Filling: Weight or volumetric methods
- Storage: 15-25°C, 35-65% RH
Soft Gelatin Capsules
- Shell: Gelatin + plasticizer (glycerin, sorbitol)
- Contents: Liquids, semi-solids, suspensions
- Manufacturing: Rotary die process
- Advantages: Unit dose liquids, improved bioavailability
- Limitations: Not for aqueous/hygroscopic fills
Powders & Granules
Powders
- Bulk powders: Large quantity, external use (dusting)
- Divided powders: Single doses, wrapped (chartulae)
- Insufflations: Nasal/throat powders
- Dentifrices: Tooth powders
- Advantages: Rapid dissolution, flexible dosing
Granules
- Definition: Aggregated powder particles (0.2-4 mm)
- Advantages: Better flow, less dust, uniform distribution
- Effervescent granules: Citric acid + sodium bicarbonate
- Uses: Oral reconstitution, direct administration
3. Liquid Dosage Forms
Solutions
Homogeneous, single-phase systems containing one or more dissolved substances (solutes) in a solvent.
| Type | Description | Examples |
|---|---|---|
| Syrups | Concentrated sugar solutions (60-80% w/v) | Simple syrup, medicated syrups |
| Elixirs | Hydroalcoholic, sweetened, flavored | Phenobarbital elixir |
| Spirits | Alcoholic solutions of volatile substances | Spirit of ammonia |
| Tinctures | Alcoholic extracts from vegetable drugs | Iodine tincture |
| Aromatic waters | Saturated aqueous volatile oils | Peppermint water |
Suspensions
Coarse dispersions of insoluble solid particles in a liquid vehicle requiring "shake well before use."
Formulation Components
- Vehicle: Structured (viscous) or flocculated
- Suspending agents: Methylcellulose, xanthan gum, CMC
- Wetting agents: Polysorbates, sodium lauryl sulfate
- Flocculating agents: Electrolytes, surfactants
- Preservatives: Parabens, benzoic acid
Quality Requirements
- • Particles settle slowly
- • Easy redispersion on shaking
- • Uniform particle size distribution
- • No caking at bottom
- • Physically and chemically stable
Deflocculated vs Flocculated: Deflocculated suspensions settle slowly but form a hard cake. Flocculated suspensions settle rapidly but redisperse easily—preferred in practice.
Emulsions
Two-phase systems of immiscible liquids (oil & water) stabilized by an emulsifying agent.
O/W Emulsion
- • Oil dispersed in water (external phase)
- • Non-greasy, washable, dilutable with water
- • Most oral emulsions are O/W
- • Emulsifier: hydrophilic (HLB 8-18)
- • Test: Dilution test (mixes with water)
W/O Emulsion
- • Water dispersed in oil (external phase)
- • Greasy, occlusive, not water-dilutable
- • Topical creams for emollient effect
- • Emulsifier: lipophilic (HLB 3-8)
- • Test: Dilution test (doesn't mix with water)
Emulsifying Agents
Surfactants
Polysorbates, Spans, SLS
Natural
Acacia, tragacanth, lecithin
Finely divided solids
Bentonite, veegum
Emulsion Instabilities
- Creaming: Reversible; globules rise/sink (density difference)
- Flocculation: Reversible; globule aggregation
- Coalescence: Irreversible; droplets merge
- Cracking: Complete phase separation (irreversible)
- Phase inversion: O/W becomes W/O or vice versa
4. Semi-solid Dosage Forms
Ointments
Semi-solid preparations for external application to skin or mucous membranes.
Ointment Bases
| Type | Components | Properties | Uses |
|---|---|---|---|
| Oleaginous | Petrolatum, mineral oil, waxes | Anhydrous, occlusive, greasy | Emollient, protection |
| Absorption | Hydrous wool fat, cholesterol | Can absorb water, forms W/O | Incorporate aqueous drugs |
| W/O Emulsion | Cold cream, rose water ointment | Contains water, occlusive | Emollient, cleansing |
| O/W Emulsion | Vanishing cream type | Non-greasy, washable | Cosmetic base, humectant |
| Water-soluble | PEG ointment (Carbowax) | Completely water-washable | Water-soluble drugs |
Creams
O/W Creams (Vanishing Creams)
- • Water-washable, non-greasy
- • Stearic acid + alkali (soap formation)
- • Spreads easily, good skin feel
- • Most cosmetic creams
- • Requires preservative
W/O Creams (Cold Creams)
- • Oily feel, occlusive
- • Beeswax + borax + mineral oil
- • Cleansing, emollient action
- • Cooling effect on evaporation
- • More resistant to microbial growth
Gels
Semi-solid systems where liquid is entrapped in a three-dimensional polymeric network.
Hydrogels (Aqueous)
- • Carbomer (Carbopol) - neutralized
- • Methylcellulose, HPMC
- • Non-greasy, clear/transparent
- • Common for topical gels
Organogels (Oleaginous)
- • Petrolatum-based
- • Plastibase (polyethylene gels)
- • Occlusive properties
- • Lipophilic drug delivery
Pastes & Suppositories
Pastes
- • High solid content (>50%)
- • Stiffer than ointments
- • Better absorption of secretions
- • Examples: Zinc oxide paste, Lassar's paste
- • Used for protective action
Suppositories
- Rectal: Cocoa butter (theobroma oil), PEG
- Vaginal: Glycerinated gelatin, PEG
- Urethral: Bougies (rare)
- • Must melt/dissolve at body temperature
- • Local or systemic effect
5. Parenteral & Sterile Products
Routes of Administration
| Route | Volume | Onset | Characteristics |
|---|---|---|---|
| Intravenous (IV) | No limit for infusion | Immediate | 100% bioavailable, no first-pass |
| Intramuscular (IM) | 1-5 mL | 10-30 min | Depot effect, suspensions OK |
| Subcutaneous (SC) | 0.5-2 mL | 15-45 min | Slower than IM, patient self-admin |
| Intradermal (ID) | 0.1-0.2 mL | Slow | Allergy testing, vaccines (BCG) |
| Intrathecal | 1-10 mL | Minutes | CNS delivery, preservative-free |
Parenteral Requirements
Mandatory Requirements
- Sterility: No viable microorganisms
- Pyrogen-free: No bacterial endotoxins (LAL test)
- Particulate-free: Clarity for IV solutions
- Isotonicity: 0.9% NaCl equivalent (usually)
- pH: Compatible range (ideally 7.0-7.4)
Parenteral Formulation
- Vehicles: WFI, normal saline, D5W
- Solubilizers: Cosolvents (PEG, propylene glycol)
- Antioxidants: Sodium metabisulfite, ascorbic acid
- Buffers: Phosphate, citrate, acetate
- Preservatives: Benzyl alcohol (multi-dose only)
Sterilization Methods
Terminal Sterilization (Preferred)
- Autoclaving:121°C, 15 psi, 15-20 min (moist heat)
- Dry heat:160-180°C, 1-2 hours (glassware, oils)
- Gamma irradiation:25 kGy (plastics, disposables)
- Gas sterilization:Ethylene oxide (heat-sensitive items)
Aseptic Processing
- Sterile filtration:0.22 μm membrane (heat-labile drugs)
- Cleanroom:ISO 5 for critical operations (Class 100)
- HEPA filters:99.97% efficiency at 0.3 μm
- Depyrogenation:250°C dry heat for glass containers
Ophthalmic Products
Requirements
- • Sterility (critical for corneal integrity)
- • Isotonicity (0.9% NaCl equivalent)
- • Buffered pH (6.5-8.5, ideally 7.4)
- • Clarity and particulate-free
- • Viscosity for retention time
Preservatives
- • Benzalkonium chloride (most common)
- • Thimerosal (mercury-based)
- • Chlorobutanol
- • Preservative-free (unit-dose)
- • Maximum 28 days after opening
6. Drug Delivery Systems
Modified Release Systems
Extended Release (ER)
- • Slower drug release than IR
- • Reduced dosing frequency
- • Matrix systems (hydrophilic/lipophilic)
- • Reservoir systems (membrane-controlled)
- • Osmotic systems (OROS)
Delayed Release
- • Drug released at specific site/time
- • Enteric coating (pH-dependent)
- • Protects acid-labile drugs
- • Protects gastric mucosa
- • Cellulose acetate phthalate, Eudragit L
Transdermal Drug Delivery
Controlled release through skin for systemic effect. Avoids first-pass metabolism and provides sustained plasma levels.
Patch Types
- Reservoir: Drug in liquid/gel compartment, rate-controlling membrane
- Matrix: Drug dispersed in polymer matrix
- Drug-in-adhesive: Drug in adhesive layer directly
- Microreservoir: Drug in microscopic spheres in matrix
Drugs Used
- • Nicotine (smoking cessation)
- • Nitroglycerin (angina)
- • Fentanyl (chronic pain)
- • Estradiol (HRT)
- • Scopolamine (motion sickness)
Ideal drug properties: MW <500 Da, log P 1-3, potent (dose <10 mg/day), non-irritating, stable at skin temperature
Novel Drug Delivery
Liposomes
- • Phospholipid vesicles
- • Encapsulate hydrophilic/lipophilic drugs
- • Targeted delivery possible
- • Reduced toxicity (doxorubicin)
- • Examples: AmBisome, Doxil
Nanoparticles
- • Size: 1-1000 nm
- • Polymeric (PLGA, chitosan)
- • Solid lipid nanoparticles
- • Enhanced permeability
- • Targeted drug delivery
Micelles & Dendrimers
- • Self-assembling structures
- • Solubilize poorly soluble drugs
- • Controlled architecture
- • Multi-functional carriers
- • Active targeting possible
Inhalation Delivery
MDI (Metered Dose)
- • Pressurized canister
- • HFA propellants
- • Requires coordination
- • Use with spacer recommended
DPI (Dry Powder)
- • Breath-activated
- • No propellants needed
- • Requires adequate flow
- • Single/multi-dose devices
Nebulizers
- • Jet or ultrasonic
- • Continuous aerosol
- • Larger volumes possible
- • Young, elderly, severe disease
7. Pharmaceutical Calculations
Percentage & Ratio Strength
Percentage Expressions
- %w/v = grams/100 mL
- %w/w = grams/100 grams
- %v/v = mL/100 mL
Ratio Strength
- 1:1000 = 1 g in 1000 mL (w/v)
- 1:1000 = 1 g in 1000 g (w/w)
- 1:1000 = 0.1%
Example Problem
How many grams of drug are in 500 mL of a 2% w/v solution?
Solution: 2% = 2 g/100 mL → (2 g × 500 mL) / 100 mL = 10 g
Dilution & Concentration
Dilution Equation
C₁V₁ = C₂V₂
(Initial concentration × Initial volume = Final concentration × Final volume)
Example
How much water must be added to 200 mL of 25% solution to make 10% solution?
Solution: C₁V₁ = C₂V₂ → (25%)(200 mL) = (10%)(V₂)
V₂ = 500 mL → Water to add = 500 - 200 = 300 mL
Alligation Methods
Used to calculate proportions when mixing two or more ingredients of different strengths.
Alligation Medial
Finds the strength of a mixture when quantities and strengths of ingredients are known.
Avg = Σ(Qty × Strength) / Σ(Qty)
Alligation Alternate
Finds the ratio of two ingredients needed to achieve a desired strength.
Parts = |Desired strength - Given strength|
Isotonicity Calculations
Solutions that exert the same osmotic pressure as body fluids (0.9% NaCl equivalent).
Sodium Chloride Equivalent Method
E value: Amount of NaCl that produces the same osmotic effect as 1 g of drug.
NaCl needed = (0.9% × Volume) - (Drug weight × E value)
Example
Make 100 mL isotonic solution with 1 g boric acid (E = 0.52).
NaCl = (0.9 × 100/100) - (1 × 0.52) = 0.9 - 0.52 = 0.38 g NaCl
Dosage Calculations
Pediatric Dosing
- Clark's Rule (weight):
Child dose = (Weight lb / 150) × Adult dose
- Young's Rule (age):
Child dose = [Age / (Age + 12)] × Adult dose
- BSA Method:
Child dose = (BSA m² / 1.73) × Adult dose
IV Drip Rate
- Drops per minute:
gtt/min = (Volume mL × Drop factor) / Time min
- Common drop factors:
- • Macrodrip: 10-20 gtt/mL
- • Microdrip: 60 gtt/mL
8. Stability & Quality Control
Drug Stability
The extent to which a product retains its physical, chemical, therapeutic, and microbiological properties within specified limits throughout shelf life.
Types of Instability
Chemical Degradation
- Hydrolysis: Water-catalyzed decomposition (esters, amides)
- Oxidation: Loss of electrons (phenols, catecholamines)
- Photolysis: Light-induced degradation (nifedipine)
- Racemization: Optical isomer interconversion
Physical Instability
- Crystallization: Solution clarity loss
- Polymorphic changes: Crystal form conversion
- Caking: Irreversible aggregation
- Cracking: Emulsion phase separation
Stability Testing (ICH Guidelines)
| Study Type | Conditions | Duration | Purpose |
|---|---|---|---|
| Long-term | 25°C ± 2°C / 60% RH ± 5% | 12-36 months | Establish shelf life |
| Intermediate | 30°C ± 2°C / 65% RH ± 5% | 6-12 months | Tropical climates (Zone IVa/IVb) |
| Accelerated | 40°C ± 2°C / 75% RH ± 5% | 6 months | Predict long-term stability |
| Stress testing | Extreme conditions | Variable | Identify degradation pathways |
Quality Control Tests
Tablet Tests
- Weight variation: USP limits based on average weight
- Hardness: Resistance to crushing (4-8 kg typical)
- Friability: % weight loss after tumbling (<1%)
- Disintegration: Time to break up in water
- Dissolution: Rate of drug release (USP apparatus)
- Content uniformity: Drug distribution in units
Parenteral Tests
- Sterility: Membrane filtration or direct inoculation
- Pyrogen test: Rabbit (fever) or LAL test
- Particulate matter: Light obscuration/microscopy
- Container integrity: Leak testing
- pH: Within specified range
- Extractables: Leachates from packaging
Packaging & Storage
Container Types
- Well-closed: Protects from extraneous solids
- Tight: Protects from air, moisture, contamination
- Light-resistant: Amber glass or opaque containers
- Hermetic: Impervious to air (ampules)
- Child-resistant: Safety packaging requirements
Storage Conditions
- Room temperature: 15-30°C (controlled)
- Cool: 8-15°C
- Refrigerated: 2-8°C
- Frozen: -25 to -10°C
- Protect from light/moisture: As specified
Expiration Dating
Based on stability data. Products must retain ≥90% of labeled potency until expiration. Beyond Use Date (BUD) applies to compounded preparations.
Key Takeaways
- ✓Excipients play critical roles: diluents, binders, disintegrants, lubricants
- ✓Direct compression, wet granulation, dry granulation—choose based on drug properties
- ✓Emulsion stability: flocculated > deflocculated; O/W for oral, W/O for topical
- ✓Parenterals must be sterile, pyrogen-free, and isotonic
- ✓Terminal sterilization preferred; aseptic processing for heat-labile drugs
- ✓Modified release: ER (prolonged), DR (delayed/enteric), CR (constant rate)
- ✓Master calculations: C₁V₁=C₂V₂, percentage, alligation, isotonicity
- ✓ICH stability: Long-term (25°C), Accelerated (40°C/75% RH for 6 months)