Tablet manufacturing process

Tablet production process

1. Tablet manufacturing process Prepared by : Avinasha S 1 st M Pharm (QA) JSSCP Submitted to: Mr Hemanth Kumar S Dept of Pharmaceutics JSSSCP

2. INTRODUCTION Tablets are commonly manufactured by wet granulation, dry granulation or direct compression. These methods may be considered to consist of a series of steps (unit processes) – weighing, milling, mixing, granulation, drying, compaction, (frequently) coating and packaging. Regardless of the method used the unit processes – weighing, milling and mixing, are the same; subsequent steps differ. 2

3. Primary goals of tablet manufacturing process To formulate tablets that are strong and hard to withstand mechanical shock encountered during manufacturing, packing, shipping, dispensing and use. To formulate tablets that are uniform in weight and in drug content. To formulate tablets that are bioavailable according to indication requirements. To formulate tablets that are chemically and physically stable over a long period of time. To formulate tablets that have elegant product identity which is free from any tablet defects. 3

4. Personnel requirements during manufacture of pharmaceutical tablets Production pharmacists/ supervisors Manufacturing chemist Analytical chemist Quality assurance manager Machine operators Mechanics 4

5. Tablet Manufacturing Equipment/ Machines Common equipment used in pharmaceutical tablet manufacturing include: Size reduction equipment e.g .,   Hammer mill , roller mill , fluidized energy mill , cutter mill and ball mill 2. Weighing balance/ balances  e.g., bulk weighing balance (weighs in kilogram), electronic weighing balance (weighs in grams and milligrams ). 5

6. 3. Mixing equipment e.g., pneumatic mixers   diffusion/ tumbling mixers  (e.g., V-blender, double cone blender, cubic mixer, drum blender),  6

7. 4. Granulators e.g. , Rotating shape granulators , dry granulator , high shear granulator etc 5. Drying equipment e.g. spray dryer , rotary dryer , fluidized bed dryer etc 6. Tableting machine e.g. single punch tablet press and multi station /rotary tablet press 7

8. 7. Quality control equipment   e.g ., disintegration equipment , USP Dissolution Tester, Tablet Hardness Tester, Tablet Thickness Tester, Tablet Friability Testers etc. 8. Coating and polishing machines for coated tablets  e.g ., standard coating pan, perforated pan, fluidized bed/ Air suspension coating system etc. 9. Packaging machines  e.g., blister packaging machines, strip packing machine, aluminium foil packaging machine, etc . 8

9. Layout of Tablets manufacturing section 9

10. Procedure for Manufacturing Tablets Dispensing:  Each ingredient in the tablet formula is weighed and accurately dispensed as per dose. This is one of the critical steps in any type of formulation process and should be done under technical supervision. Sizing:  Formulation ingredients must be in finely divided form, otherwise, size reduction should be carried out for better flow property and easy mixing . 10

11. Powder blending:  Powders are mixed using a suitable blender to obtain a uniform and homogeneous powder mix. The drug substance and excipients are mixed in geometric dilution. Granulation:  Here small powder particles are gathered together into layers, and permanent aggregates to render them into free-flowing states. Drying and dry screening:  Screened wet granules need to be dried for a particular time period in tray dryer or fluid bed dryer at controlled temperature not exceeding 550 degree C . Dried granules are screened through the appropriate mesh screen 11

12. Tablet compression:  This step involves the compression of granules into a flat or convex, round, oblong, or unique shaped, scored or unscored tablets; engraved with an identifying symbol and/ or code number using  tablet press . Coating:  Tablets and granules are coated if there is need to mask the unpleasant taste/odour of some drug substance or to increase the aesthetic appeal of uncoated tablets as well as to modify the release or control the release of drug substance from tablets. This is achieved by enclosing or covering the core tablet or granules with coating solutions. 12

13. Methods used in tablet Formulation Tablets are commonly manufactured by Wet granulation Dry granulation or Direct compression 13

14. WET GRANULATION Wet granulation is a widely used method for the production of compressed tablet. It is essentially a process of size enlargement involving several steps and the use of an adhesive substance known as binder . The granules produced using this method of granulation has a greater probability of meeting all the physical requirements for tablet formation . 14

15. FLOW CHAT OF WET GRANULATION 15

16. Methods: 1. Weighing , milling and mixing of the APIs with powdered excipients (excluding the lubricant) 2. Preparation of binder solution 3. Mixing of binder solution with powders to form a damp mass 4. Screening the dampened powder into pellets or granules (wet screening) using 6- to 12-mesh screen 5. Drying of moist granules 16

17. 6. Sizing the granulation by dry screening using 14- to 20-mesh screen 7. Mixing of the dried granules with lubricant and disintegrates 8. Compression of granules into tablets 17

18. DRY GRANULATION The formation of granules by compacting powder mixtures into large pieces or compacts which are subsequently broken down or sized into granules (often referred to as dry granulation, double compression or pre-compression) is a possible granulation method which, however, is not widely used in the manufacture of tablets. 18

19. Flow chat of dry granulation 19

20. D ry granulation method Weighing and Milling of formulation ingredients (drug substance and excipients) Mixing of milled powders. Compression of mixed powders into slugs. Milling and sieving of slugs. Mixing with disintegrate and lubricant. Compression into tablet . 20

21. DIRECT COMPRESSION direct compression involves direct compression of powdered materials into tablets without modifying the physical nature of the materials itself. Direct compression avoids many of the problems associated with wet and dry granulations. 21

22. Its successful application in tablet formulation rests on two fundamental issues : The availability of suitable excipients The availability of suitable machinery. 22

23. Flow chat of direct compression 23

24. D ry granulation method . Milling of therapeutic agent and excipients Mixing of milled powders, disintegrates and lubricants Compression into tablet 24

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26. Quality control of tablets O fficial tests Content of active ingredient/ absolute drug content test/ assay of active ingredient. Weight uniformity test/ weight variation test Content uniformity test Disintegration time test Dissolution test 26

27. 27 UNIFORMITY OF CONTENT As per IP : 10mg / less than 10% w/w of active ingredient As per BP/USP : 25mg /less than 25%w/w DISINTEGRATION TEST As per IP : 28-32 cycle per min As per BP/USP : 29-32 cycle per min

28. Disintegration testing condition and interpretation (IP) Sr. No Type of tablets Medium Temperatu re Limit 1 Uncoated Water/buffer 37 °±  2 °C 15 min or as per individual monograph 2 Film coated Water 37 °±2 °C 30 min or as per individual monograph 3 Sugar coated Water/0.1 N HCl 37 °±2 °C 60 min or as per individual monograph 4 Dispersible Tablets Water 25 °±1 °C 03 min or as per individual monograph 5 Effervescent Tablets Water 25 °±5 °C 05 min or as per individual monograph 6 Enteric-coated Tablets 0.1 M HCl mixed phosphate buffer pH 6.8 37 °±2 °C 02 hour in HCl: no disintegration 60 min in buffer : disintegrate 7 Soluble Tablets Water 20 °±5 °C 03 minutes

29. Disintegration testing condition (USP) Sr. No Type of tablets Medium Temperatu re Limit 1 Uncoated Water/as specified in monograph 37 °±  2 °C As per individual monograph 2 Coated Water/as specified in monograph 37 °±2 °C As per individual monograph 4 Enteric-coated Tablets Simulated gastric fluid TS Simulated intestinal fluid TS 37 °±2 °C 01 hour in Simulated gastric fluid As per individual monograph: Simulated intestinal fluid TS 5 Buccal Tablets Water/as specified in monograph 37 °±  2 °C 4 hour 6 Sublingual tablets Water/as specified in monograph 37 °±  2 °C As per individual monograph

30. non-official tests hardness test Friability test 30

31. Packaging and storing of tablets Before tablets are sent out for distribution, they are usually packaged using appropriate packaging materials. The type of packaging material used is a matter of choice and is dependent on several factors including: The degree of protection required Compatibility of the packaging material with the formulation. 31

32. Presentation, particularly for those products which may be the subject of impulse buying Customer convenience in terms of size, weight, method of opening or reclosing legibility of printing, etc. Filling method and Cost 32

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