Tablet Manufacturing and Excipients

Tablets are the most widely used oral dosage form, accounting for approximately 70% of all pharmaceutical preparations. Their dominance stems from dose precision, manufacturing scalability, stability, and patient acceptability. Understanding tablet formulation requires detailed knowledge of excipient functions, manufacturing processes, and quality control parameters.

Tablet excipients are broadly categorised by function. Diluents or fillers provide bulk to the tablet mass when the active pharmaceutical ingredient (API) dose is small. Microcrystalline cellulose (MCC, Avicel) is the gold-standard diluent, offering compressibility and acting as a dry binder. Lactose monohydrate is widely used but unsuitable for lactose-intolerant patients or APIs susceptible to Maillard reactions. Dibasic calcium phosphate provides good flow and compressibility but is alkaline, limiting use with acid-labile drugs.

Binders hold tablet particles together to form a coherent compact. Dry binders such as MCC function during direct compression. Wet binders are dissolved in granulating fluid; polyvinylpyrrolidone (PVP, Povidone) and hydroxypropyl methylcellulose (HPMC) are common. Binder concentration critically affects tablet hardness and dissolution — excess binder impedes disintegration and drug release.

Disintegrants promote tablet break-up in gastrointestinal fluid. Sodium starch glycolate (Explotab) and croscarmellose sodium (Ac-Di-Sol) are superdisintegrants that swell rapidly on water uptake, generating internal stress that fractures the tablet matrix. Crospovidone acts by wicking and capillary action rather than swelling. The mechanism matters: swelling disintegrants perform poorly in hydrophobic matrices where water access is limited.

Lubricants reduce friction between tablet and die wall during ejection. Magnesium stearate is ubiquitous at 0.25–1% concentration. It is hydrophobic and reduces wettability; over-mixing causes over-lubrication, reducing tablet hardness and dissolution rate. Sodium stearyl fumarate (Pruv) is a hydrophilic alternative with less sensitivity to mixing time. Glidants such as colloidal silicon dioxide (Aerosil) improve powder flow by reducing inter-particle friction.

Tablet manufacturing follows three main processes. Direct compression blends all components and compresses without prior granulation — simplest and cheapest, but requires free-flowing, compressible powders. Wet granulation adds granulating fluid to form granules, improving flow and compressibility. It is the most robust process for cohesive powders but adds cost and moisture exposure. Dry granulation (roller compaction or slugging) is preferred for moisture-sensitive APIs — powder is compacted into ribbons then milled to granules without liquid.

Compaction mechanics involve two stages: rearrangement and deformation. Plastic deformation (MCC, starch) creates strong compacts; brittle fracture (lactose, DCP) increases surface area for bonding. Mixed mechanisms are common. Tensile strength, friability, and disintegration time are primary quality attributes.

Film coating is applied for taste masking, moisture protection, modified release, or improved appearance. Immediate-release coatings use HPMC or polyvinyl alcohol (PVA). Enteric coatings (cellulose acetate phthalate, Eudragit L/S) resist gastric acid but dissolve at intestinal pH, protecting acid-labile drugs or targeting colonic delivery.

Quality control of tablets encompasses weight variation (BP ±5% for most tablets), hardness (typically 4–8 kP for conventional tablets), friability (<1% loss after 100 rotations per BP), disintegration (<15 min for uncoated tablets), and dissolution testing using USP apparatus I (basket) or II (paddle). The f2 similarity factor compares dissolution profiles; f2 ≥ 50 indicates similarity.