Tablet Dosage Form PDF

Tablet Dosage Form Lecturer: Dr Bahjat Alhasso PhD Pharmaceutics [email protected]  INTRODUCTION Tablets are solid preparations each containing single dose of one or active ingredients and usually obtained by compressing uniform volume of particles. Ta...

Tablet Dosage Form Lecturer: Dr Bahjat Alhasso PhD Pharmaceutics [email protected]  INTRODUCTION Tablets are solid preparations each containing single dose of one or active ingredients and usually obtained by compressing uniform volume of particles. Tablets can be administered by 1. Swallowing whole 2. Chewing 3. Retaining in the mouth (melt-in-mouth) 4. Buccal - designed to release the drug slowly 5. Sublingual - designed for fast action 6. Dissolve or disperse first in water before administration  Tablets normally contain excipients in addition to the active ingredients Tablets are mainly used for systemic drug delivery Sometimes can be local drug delivery e.g vaginal tablets Drug must be released first before being absorbed Need to break down to small pieces(disintegration) Need to dissolve (dissolution) Formulation strongly influence these parameters  ADVANTAGES: 1. Oral route is convenient and a safe way of drug administration 2. Better physical and chemical stability than liquid dosage forms 3. Accurate dosing of the drug (fixed dose per tablet) 4. Convenient to handle and use (patient’s preference) 5. Production procedures can be quality-controlled 6. Mass production, low cost DISADVANTAGES: 1. Poor bioavailability of poorly water-soluble drugs or poorly absorbable drugs 2. Difficult to swallow for some patients etc.  QUALITY ATTRIBUTES OF TABLETS 1. Elegant in appearance, characteristic shape, colour 2. Consistent in weight and size 3. Correct dose 4. Uniform in drug content 5. Biocompatible (no toxic excipients) 6. Sufficient mechanical strength to withstand handling during manufacture, packaging, transportation and use 7. Physically, chemically and biologically stable 8. Drug should be released in a reproducible manner 9. Must be bioavailable (disintegration and dissolution) 10. Acceptable by the patient for the intended use 11. Must retain all the functional attributes, which include drug stability and efficacy  TABLET MANUFACTURING Normally tablets are formed by forcing particles into close proximity to each other by powder compression, so that the particles cohere into a porous solid of defined shape. Powder compression: reduction of volume of a powder due to the application of a force Powder compaction: the formation of solid specimen of defined geometry by powder compression.  PARTS OF A SINGLE PUNCH TABLETING MACHINE 1. Hopper for storing and feeding the granules 2. Feed frame for distributing the formulation into the dies 3. Dies for controlling the size and shape of the tablet 4. Punches for compacting the formulation into tablets 5. Cams that act as tracks to guide the moving punches WORKING OF SINGLE PUNCH TABLET MACHINE  WORKING OF SINGLE PUNCH TABLET MACHINE 1. The filling stage: powder fills the die by gravity or centrifugal force 2. The compression stage: the upper punch lowers into the die and the powder is compressed; then upper punch moves up 3. The ejection stage: lower punch moves up to reject Tablet weight (amount of material filled into the die) is controlled by the position of the lower punch Lower punch remains stationary during compaction About 200 tablets per min  STEPS IN WORKING OF ROTARY TABLETING MACHINE Many dies on the die table and many pairs of punches (upto 60) Die table and punches rotate together, i.e.the same punch always works with the same die 10000 tablets per min can be achieved Suitable for mass production WORKING OF ROTARY TABLET MACHINE  http://en.wikipedia.org/wiki/File:Tablet_press_animation.g if http://www.youtube.com/watch?feature=player_detailpage &v=h2fnpl-Bkvk  INSTRUMENTED TABLET PRESS 1. Forces during compression are recorded 2. Forces from the upper and lower punches 3. Forces transmitted to the die 4. Displacement of the upper and lower punch during the compression and decompression phase recorded Used in research. Normally instrumented single-punch or hydraulic presses (also called compaction simulator) are used 1. Useful to investigate the relation between applied force and the properties of tablets produced 2. To describe and analyse compression properties of powders by recording punch forces and punch displacement  TABLET PRODUCTION VIA GRANULATIONS Reasons for granulation for tableting: 1. To improve flowability of the powder 2. To improve mixing homogeneity and reduce segregation 3. To improve the compactability of the powder (e.g.by adding a binder) 4. To improve the bulk density of the powder 5. To ensure a homogeneous colour of the tablets 6. To improve dissolution of poorly soluble drugs by dispersing fine powders of the drug in hydrophilic diluent Flow chart showing unit operation in tableting with precompaction treatment by wet granulation Unit operation in tableting with precompaction treatment by dry granulation  LIMITATIONS OF GRANULATION 1. Large number of processing steps 2. Large area required 3. Requires a number of equipment 4. Production time is long, especially wetting and drying steps 5. Consumes energy in the drying process in wet granulation 6. Stability problems in wet granulation (some drugs are not stable in wet condition and when heated in the drying process) 7. High cost  DIRECT COMPRESSION Direct compression is process by which the tablets are compressed directly from powder blends of active ingredients and suitable excipients Advantages 1. Simplified production procedure 2. There are only two steps in operation :powder mixing and tableting 3. Reduced production time 4. Reduced consumption of energy 5. Low cost due to the reduction in production time and energy 6. Optimised drug dissolution 7. Less stability issue (no solvent and heat involved)  Limitations or disadvantages of direct compression: 1. Need special grades of excipients (more expensive) 2. Higher risk of powder segregation 3. Powders of high drug content is difficult to form into tablets, if the drug has poor compactability  DIRECT COMPRESSION Direct compaction has been used mainly for two types of drugs 1. Drugs that have good flowability (e.g. powders with large size) 2. Potent drugs that are of low content (e.g. a few mg) in the tablet. In direct compression, the powder properties are mainly controlled by the excipients. Special grade directly compressible diluents used for the process  TABLET EXCIPIENTS 1. Diluent (or bulking agent) 2. Binding agent (binder) 3. Disintegrant 4. Glidant 5. Lubricant 6. Anti-adherent 7. Sorbent 8. Taste adjusting agent 9. Flavoring agent 10. Colorant  DILUENTS Low dose drugs need diluent (filler) so that tablets of certain weight can be produced Desired feature of an ideal diluent 1. Biocompatible (non-toxic, non irritant etc) 2. Chemically inert 3. Non-hygroscopic 4. Water soluble or hydrophilic 5. Good compressibility 6. Good dilution capacity 7. Acceptable taste 8. Acceptable to regulatory agencies 9. Physically and chemically stable 10. Commercially available 11. Low cost All these requirements cannot be met by a single excipient. There are many different excipients to choose from.  DILUENTS 1. Lactose The most common filler in tablets Dissolves readily in water Pleasant taste Available as anhydrous and crystalline form Anhydrous lactose dissolves faster than crystalline Anhydrous lactose posses excellent compaction properties, so used for direct compression Spray dried lactose, fast flow lactose for direct compression  Disadvantage : intolerant to some people Anhydrous lactose may spontaneously convert to the more stable crystalline form, at suitable conditions. E.g. high temp and humidity. 2. Glucose, Dextrose Often used in chewable tablets Sucrose Used as a sweetener / diluent in effervescent tablets and chewable tablets 3. Mannitol Good taste used in chewable tablets Negative heat of solution giving cooling sensation in the mouth  DILUENTS 4. Microcrystalline cellulose Prepared by hydrolysis of cellulose followed by spray drying Particles formed are aggregates of smaller cellulose fibres The particles have crystalline and amorphous regions The crystallinity may vary depending on the source of the cellulose and preparation procedure The crystallinity will affect the properties of the particles, including hygroscopicity and powder compactability Biocompatible Inert Good disintegrating property Good compactability (can be used as dry binders) Suitable for direct compression Disadvantage: hygroscopic 5. Dicalcium phosphate Cheap Water insoluble Non hygroscopic Hydrophilic, wetted by water Good flow, suitable for direct compression  BINDERS Also called as adhesive added to drug-filler to ensure that tablets be formed with the required mechanical strength. A binder can be added: as dry powder added to powder before wet granulation as a solution used to produce wet granules (solution binder) as a dry powder which is mixed with other powder before compaction (dry binder) Solution binders are the best E.g. PVP, Starch, HPMC, Ethyl cellulose Up to 2-10% by weight.  DISINTEGRATANT Added to the formulation to ensure that the tablet breaks up to small particles, when in contact with liquid Mechanisms by which it works: 1. Facilitate water uptake, i.e. helps to transport water into the pores of the tablets. 2. Wetting of surface by surfactants. 3. Capillary forces to suck water into tablets. 4. Rupture the tablets by swelling of the disintegrant. 5. Deformed particles restore to their original shape upon contact with water. 6. Particle repulsion upon contact with water.  DISINTEGRANTS 1. Starch (potato, corn and maize) The most common one in traditional tablets Swell upon in contact with water, Used Up to 10% 2. Microcystalline Cellulose 3. Modified starch 4. Primogel Sodium Starch Glycolate 5. Modified cellulose 6. Cross caramellose internally cross-linked sodium 7. Carboxymethylcellulose 8. Gas generating disintegrant Bicarbonate or carbonate salts together with weak food – acid, E.g. citric acid and tartaric acid CO2 is generated when in contact with water Used in effervescent tablets DISINTEGRANTS  GLIDANTS Advantages of glidants: 1. To improve the flowability of the powders/granules 2. Improve flow by adhering to the surface of other particles and reducing interparticulate friction Examples 1. Colloidal silica (very small particle size),Used in low quantity (about 0.2%) 2. Magnesium stearate can also improve powder flow 3. Talc 1-2 %  LUBRICANTS To ensure low friction between tablets and die wall. High friction may result in: – vertical scratches on tablet edges – capping or fragmentation of tablets during ejection process Mechanisms of lubrication 1. Fluid lubrication - rarely used e.g. Liquid paraffin in effervescent tablets 2. Boundary lubrication - fine particulate solid e.g. Magnesium stearate (most widely used) – It is used in low quantity (