Tablet Manufacturing Overview

Tablet Manufacturing

• Learning outcomes include discussion of compacted tablets' advantages and disadvantages as a pharmaceutical dosage form, identification of key tablet quality attributes, explanation of excipient uses in formulations, tablet classification, and explanation of compression and compaction mechanisms.
• Tablets were patented in 1843. The initial machine consisted of a metal die with a hole drilled through it, which compressed powder between cylindrical punches. It was first used to produce potassium bicarbonate compacts.
• Tablets are solid preparations containing one or more active substances. They are obtained by compressing uniform volumes of particles or by other methods like extrusion, moulding, or freeze-drying.
• Advantages of tablets include large-scale, low-cost production, easy packaging and transport, high stability compared to liquids, and ease of handling for patients, doctors, and pharmacists.
• Disadvantages include inability to use during unconsciousness or vomiting, potential for tablets to cement during long-term storage, and a series of unit operations during manufacturing. Tablets may include harmful auxiliary substances, have slow action, or exhibit poor bioavailability for poorly water-soluble/absorbed drugs, and potential for local irritation from API.
• Desired tablet attributes include correct API dose, elegant appearance, consistent weight/size/appearance, controlled reproducible release, biocompatibility, sufficient mechanical strength, microbiological stability, patient acceptability, and safe packaging.
• Different types of tablets exist, including oral, vaginal, and implantation (pellets).
• Immediate release tablets include chewable, effervescent, coated, sugar-coated, film-coated, enteric-coated, buccal, sublingual, and controlled release tablets.
• Dissolution and absorption of tablets are affected by factors like API solubility, addition of salts during dissolution, API surface area, lipophilicity, and substances that alter GIT cell membrane permeability and absorption enhancers.
• Chewable tablets, compressed lozenges, and effervescent (carbonate/bicarbonate reaction with weak acid) tablets have specific characteristics.
• Buccal and sublingual tablets are small, flat, and oval, dissolve and absorb in the mouth, and skip the first-pass metabolism in the liver.
• Coated tablet types include sugar-coated, film-coated, and enteric-coated tablets with various uses like masking tastes, providing colour, and protecting ingredients.
• Excipients are inert materials within tablets, categorized for their role in processing (e.g. diluents, binders, disintegrants, lubricant) or for physical characteristics (e.g. colours, flavours).
• Diluents like lactose, kaolin, and calcium phosphate ensure bulk and accurate dosing in tablets, important especially for low-dose API formulations.
• Binders maintain the integrity for the tablet and are responsible for maintaining granules.
• Disintegrants ensure the breakup of tablets into smaller particles, with important mechanisms facilitating water uptake and tablet rupture.
• Lubricants reduce friction (avoid tablet adhesion), optimize pressure distribution during compression, and increase density before compression. Glidants improve powder flow.
• Antiadherents prevent tablet adhesion to dies or presses, and helpful for engraved punches.
• Adsorbents are used when liquid or semi-solid components are in the formulation, while sweetening agents are added for taste improvement for unpalatable API.
• Flavours/colours/fragrances are added to tablets for better taste and appearance. Surface active agents enhance the wettability and dissolution rates of API or other excipients.
• Different tablet manufacturing methods exist, including granulation and direct compression. Granulation involves forming granules from powders (wet or dry), while direct compression involves directly compressing powders without granulation.
• Tablet machines are classified. Granulation, direct compression, different types of presses, etc.
• Tablet quality standards include appearance, friability, resistance to crushing, uniformity in mass and content. Common defects include weight variation, friability variation, picking and sticking, capping and lamination, chipping, and double pressing.
• Important factors when controlling weight variability include product uniformity in particle size, uniformity in particle density, proper setup of the tablet press, and flow rates into the die cavity.
• Issues like friability, picking/sticking, capping, and lamination or chipping are common issues during tablet manufacturing. These issues need careful consideration in machine operations and powder formulation.
• Double impressions can occur when punches twist or jump during compression.
• Different types of tablet coatings like sugar coatings, and film coatings exist with various purposes, including protection and masking.
• There are processes for coating tablets that involve spraying a solution to create films.
• Coating process involves loading tablets, tumbling, and introducing warm air for drying.
• Factors for milling include mechanical energy, and the various mills used for different purposes and stages of processing.
• The final blend is the outcome of the granulation, dispensing, and lubrication phases. Blending time, uniformity, and lack of segregation are key considerations for quality.