Tablets & Capsules Masterclass for Competitive Exams
Subject: Pharmaceutics
Subject: Pharmaceutics
Tablets are solid dosage forms containing medicinal substances with or without suitable excipients. They are typically prepared by compression or, less frequently, by molding. They vary in size, shape, weight, hardness, thickness, disintegration, and dissolution characteristics.
| Advantages | Disadvantages |
|---|---|
| Most common, economical, and stable dosage form. | Some drugs resist compression into compacts. |
| Accurate and precise dosage. | Poorly wetting drugs, slow-dissolving drugs, or large dose drugs may have bioavailability issues. |
| High patient acceptance (convenient to take, compact). | Drugs with objectionable taste/odor or highly potent drugs may require coating. |
| Masks unpleasant tastes (with coating). | Difficulty in swallowing for some patients (pediatric, geriatric). |
| Can be designed for various release patterns (sustained, enteric). | Not suitable for drugs that are highly hygroscopic or deliquescent. |
| Type | Description | Exam Focus / Examples |
|---|---|---|
| Compressed Tablets | Formed by compression, without coating. | Most common type; Paracetamol tablets. |
| Multiple Compressed Tablets (MCTs) | Layered (tablet-in-tablet) or compressed coated. Separate layers for incompatible drugs or staged release. | Example: Buprenorphine/Naloxone (layered), multiple release profile drugs. |
| Sugar-Coated Tablets (SCTs) | Coated with a sugar layer; elegant, masks taste, protects drug. | Process is lengthy, adds weight/bulk; many older formulations. |
| Film-Coated Tablets (FCTs) | Coated with a thin polymer film; more durable, less bulky than sugar coat, faster processing. | Polymer examples: HPMC, Methylcellulose, Ethylcellulose. Most modern coated tablets. |
| Enteric-Coated Tablets | Resist gastric fluid, disintegrate in intestinal fluid. Protects acid-labile drugs or stomach from irritation. | Coating polymers: Cellulose Acetate Phthalate (CAP), Eudragit L, HPMC phthalate. Aspirin, Omeprazole. |
| Chewable Tablets | Intended to be chewed, useful for pediatric/geriatric patients. Pleasant taste. | Often contain mannitol, xylitol as excipients. Antacids, certain antibiotics. |
| Buccal Tablets | Placed in the buccal pouch, dissolves slowly, absorbed through buccal mucosa. Avoids first-pass metabolism. | Example: Fentanyl buccal tablets. |
| Sublingual Tablets | Placed under the tongue, dissolves rapidly, absorbed through sublingual mucosa. Rapid onset, avoids first-pass. | Example: Nitroglycerin for angina. |
| Effervescent Tablets | Contains acid (citric, tartaric) and base (sodium bicarbonate); releases CO2 upon contact with water, rapidly disperses. | Antacids, Vitamin C. Ensure anhydrous storage. |
| Orally Disintegrating Tablets (ODT) | Disintegrate rapidly in the mouth (seconds) without water. Enhanced patient compliance. | Technologies: Lyophilization, spray drying, sublimation. Example: Ondansetron ODT. |
| Vaginal Tablets (Inserts) | Ovoid shaped, for local effect in the vagina. | Antifungals (Clotrimazole), Hormonal (Estradiol). |
| Excipient Class | Function | Common Examples | Exam Specifics |
|---|---|---|---|
| Diluents/Fillers | Add bulk to make the tablet a suitable size. | Lactose (anhydrous, monohydrate), Microcrystalline Cellulose (MCC - Avicel), Dibasic Calcium Phosphate (DCP), Mannitol, Sorbitol. | Lactose is most common. MCC acts as diluent, disintegrant, binder. Mannitol/Sorbitol for chewables. |
| Binders/Adhesives | Impart cohesiveness to powder particles, ensuring tablet integrity. | Starch paste, Gelatin, PVP (Povidone), HPMC, CMC-Na, Acacia, Tragacanth, Sodium Alginate. | PVP is synthetic, good for wet granulation. Starch paste common. |
| Disintegrants | Promote tablet breakup into smaller particles in aqueous media. | Starch, Croscarmellose Sodium (Ac-Di-Sol), Sodium Starch Glycolate (SSG - Primojel), Crospovidone, Alginates. | Superdisintegrants (Croscarmellose, SSG, Crospovidone) used at low concentrations (2-5%). |
| Lubricants | Reduce friction between tablet and die wall/punch during ejection; prevent sticking. | Magnesium Stearate, Stearic Acid, Talc, PEG, Sodium Stearyl Fumarate. | Magnesium Stearate is most common but hydrophobic, can affect disintegration/dissolution. Talc is also a glidant. |
| Glidants | Improve flow properties of granules/powder by reducing inter-particulate friction. | Colloidal Silicon Dioxide (Aerosil), Talc, Corn Starch. | Aerosil is very effective at low concentrations (0.1-0.5%). |
| Anti-adherents | Prevent sticking of tablet material to punch faces. | Talc, Magnesium Stearate, Corn Starch. | Often overlap with lubricants/glidants. |
| Colorants | Enhance appearance, aid in product identification. | Iron oxides, Titanium Dioxide (opacifier), synthetic dyes (e.g., FD&C Yellow #6). | Must be approved for pharmaceutical use. |
| Flavorants/Sweeteners | Mask objectionable taste, especially for chewable/ODT. | Flavoring oils (peppermint, cherry), Sucrose, Aspartame, Saccharin, Mannitol, Xylitol. | Mannitol/Xylitol are also diluents and provide a cooling sensation. |
| Defect | Description | Probable Cause(s) | Remedy / Exam Tip |
|---|---|---|---|
| Capping | Partial or complete separation of the top or bottom layers of the tablet. | Air entrapment, deep concave punches, excessive fines, insufficient binder, too rapid compression. | Reduce compression speed, optimize binder, use flat punches, reduce fines, pre-compression. |
| Lamination | Separation of tablet into two or more distinct layers. | Similar to capping, often more severe. Caused by elastic recovery on ejection. | Adjust compression, modify granulation (binder/size), reduce lubricant. |
| Picking | Small amounts of material stick to the punch face, usually upper punch. | Excessive moisture in granules, low melting point ingredients, rough punch faces. | Optimize moisture content, use chilling dies, polish punch faces, increase lubricant. |
| Sticking | Tablet material adheres to die walls (wider area than picking). | Excessive moisture, too much binder, insufficient lubricant, high compression force. | Reduce moisture, optimize binder, increase lubricant, reduce compression. |
| Mottling | Uneven distribution of color on the tablet surface. | Differences in color of drug/excipients, improper mixing, dye migration during drying. | Use uniform colorants, improve mixing, use adsorption colorants, optimize drying. |
| Weight Variation | Inconsistent weight among tablets. | Poor powder flow, segregation of granules, uneven die filling, worn punches/dies. | Improve flow (glidant), ensure uniform particle size, check equipment. |
| Hardness Variation | Inconsistent hardness among tablets. | Weight variation, uneven die filling, inconsistent compression force. | Control weight, check machine calibration. |
| Double Impression | Occurs with engraved punches; punch makes a second impression on tablet surface. | Free rotation of upper punch during ejection, no anti-turning device. | Use anti-turning devices (keying) on punches. |
| Test | Purpose | Method / Apparatus | Compendial Limits (GPAT Focus) |
|---|---|---|---|
| Appearance | Visual check for color, shape, size, surface texture, defects. | Visual inspection. | Consistent within batch. |
| Size & Shape | Ensures uniformity. | Micrometer, Vernier caliper. | Within specified dimensions. |
| Hardness (Crushing Strength) | Resistance to fracture, indicates structural integrity. | Monsanto, Pfizer, Strong-Cobb, Schleuniger, Erweka hardness testers. | Typically 4-10 kg/cm² (may vary by formulation). |
| Friability | Tablet's ability to withstand abrasion during handling and packaging. | Roche Friabilator (rotated for 100 revolutions in 4 minutes). | NMT 1% weight loss is generally acceptable. |
| Weight Variation | Ensures uniformity of drug content. | Weigh 20 tablets individually, calculate average, compare individual weights. | USP/IP Limits: Average weight ≤ 130 mg: ±10% 130 mg to 324 mg: ±7.5% > 324 mg: ±5% |
| Disintegration Time | Time required for a tablet to break up into particles. | Disintegration Apparatus (basket-rack assembly with 6 tubes, immersed in specified medium at 37°C). | Uncoated: 15 min Film-Coated: 30 min Sugar-Coated: 60 min Effervescent: 5 min Enteric: No disintegration in acid (2hr), then <60 min in intestinal fluid. |
| Dissolution Rate | Rate at which the drug dissolves from the tablet into a dissolution medium. Critical for bioavailability. | Dissolution Apparatus (USP Apparatus 1: Basket, USP Apparatus 2: Paddle). | Specified in individual monographs (e.g., NLT 80% dissolved in 30 min). |
| Content Uniformity | Ensures uniform distribution of API in low-dose or highly potent tablets. | Assay 10 individual tablets. | Required if drug content is <25 mg or <25% of tablet weight. Individual contents should be within 85-115% of average. |
Capsules are solid dosage forms in which the drug substance is enclosed in a soluble shell, typically made of gelatin. They are elegant, tasteless, and easily swallowed.
| Advantages | Disadvantages |
|---|---|
| Elegant appearance, easily swallowed, masks taste/odor. | More expensive than tablets. |
| Faster drug release than compressed tablets (generally). | Highly soluble salts (KCl) may cause gastric irritation due to rapid localized release. |
| Flexible formulation; can enclose powders, liquids, pellets, tablets. | Not suitable for highly efflorescent (release water) or deliquescent (absorb water) materials. |
| Good for potent drugs requiring low doses (diluted with inert material). | Shells susceptible to moisture and extreme temperatures. |
| Protects photosensitive drugs. | Filling equipment for capsules is generally slower than tablet presses. |
HGCs consist of two parts: a body and a cap. The shells are made primarily from gelatin.
SGCs are hermetically sealed, single-unit solid dosage forms. They are generally thicker than HGCs and contain plasticizers (e.g., Glycerin, Sorbitol) in the gelatin shell to keep them flexible.
| Test | Purpose | Method / Apparatus | Compendial Limits (GPAT Focus) |
|---|---|---|---|
| Appearance | Visual check for defects, shape, color, uniform sealing. | Visual inspection. | Consistent within batch. |
| Weight Variation | Ensures uniformity of fill weight. | Weigh 20 capsules, remove contents, reweigh empty shells, calculate net fill weight. | USP/IP Limits: Average weight ≤ 300 mg: ±10% > 300 mg: ±7.5% |
| Disintegration Time | Time required for capsule shell to break apart. | Disintegration Apparatus (same as tablets, often with discs). | Hard & Soft Gelatin: NMT 30 min (unless otherwise specified). |
| Dissolution Rate | Rate at which the drug dissolves from the capsule. | Dissolution Apparatus (USP Apparatus 1: Basket, USP Apparatus 2: Paddle). | Specified in individual monographs. |
| Content Uniformity | Ensures uniform distribution of API in low-dose or potent capsules. | Assay 10 individual capsules. | Required if drug content is <25 mg or <25% of fill weight. |
| Moisture Content (Shell) | For HGC shells, excessive moisture makes them soft; too little makes them brittle. | Karl Fischer titration, Loss on Drying (LOD). | HGC: 13-16%; SGC: 20-30% (for plasticity). |
| Leak Test (for SGCs) | Detects leaks in sealed soft gelatin capsules. | Place in dye solution, apply vacuum; presence of dye inside indicates leak. | No signs of leakage. |
| Feature | Tablets | Capsules |
|---|---|---|
| Manufacturing Speed | Generally faster (up to 1 million/hr) | Slower (up to 150,000/hr) |
| Cost of Manufacturing | Lower per unit | Higher per unit (shell cost, slower filling) |
| Patient Acceptance | Good, but swallowing can be an issue for some. | Generally excellent (smooth, easy to swallow), masks taste/odor. |
| Flexibility of Formulation | Limited to solid or semi-solid components. | High; can encapsulate powders, granules, pellets, semi-solids, non-aqueous liquids. |
| Bioavailability | Can be slower due to compaction force, but can be tailored. | Often faster due to rapid disintegration of shell and no compression. |
| Stability | Good, but can be compromised by hygroscopic excipients. | Good, but sensitive to moisture (HGCs) or can interact with aqueous fills (SGCs). |
| Protection of Drug | Can be coated for protection (light, moisture, acid). | Gelatin shell protects; SGCs are hermetically sealed. |
| Compaction Issues | Subject to defects like capping, lamination. | Not applicable, but issues with fill material flow or sealing. |
| Size Limits | Dependent on compression force and die size. | Dependent on capsule shell size (e.g., #000 (largest) to #5 (smallest) for HGCs). |
| Suitability for Hygroscopic/Deliquescent Drugs | Difficult, as they can cause issues during compression. | Generally unsuitable, can extract water from or provide water to the shell. |
| Special Release Forms | Extensive (ER, DR, chewable, ODT, buccal, sublingual). | Extended release possible with modified pellets; enteric coating applied to pellets inside. |
| Test / Parameter | Standard Limit / Value | Relevance |
|---|---|---|
| Tablet Friability (Roche Friabilator) | NMT 1% weight loss after 100 revolutions. | Measures resistance to abrasion; higher values indicate fragile tablets. |
| Hardness (Crushing Strength) | 4-10 kg/cm² (general range) | Indicates mechanical strength; affects handling and disintegration. |
| Disintegration Time (Uncoated Tablets) | NMT 15 minutes | Crucial for drug release; determines how quickly tablet breaks down. |
| Disintegration Time (Hard/Soft Gelatin Capsules) | NMT 30 minutes | Ensures prompt release of capsule contents. |
| Disintegration Time (Enteric Coated Tablets) | No disintegration in acidic medium (2 hrs); disintegration in intestinal fluid (NMT 60 min). | Ensures drug protection from stomach acid and release in intestines. |
| Content Uniformity Requirement | Required if drug content <25 mg OR <25% of total tablet/capsule weight. | Ensures consistent drug dose, especially for potent or low-dose drugs. |
| Moisture Content of HGC Shells | 13-16% w/w | Maintains flexibility; deviation causes brittleness (low moisture) or softness (high moisture). |