Pharmaceutical Manufacturing Technique PPT

Manufacturing, flow chart and IPQC of tablet

1. M. Pharm Sem-I Presentations Title: manufacturing and manufacturing flowchart and IPQC of tablet SUBMITTED TO SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE FOR PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF MASTER OF PHARMACY IN THE SUBJECT Pharmaceutical Quality Assurance IN THE FACULTY OF SCIENCE AND TECHNOLOGY Bhujbal Knowledge City, MET’s Institute of Pharmacy, Adgaon, Nashik, 422003. Maharashtra, India Academic Year-2021-2022 1 Presented By- Prajakta Sanjay thorat Guided By : Dr. s. p. ahirrao

2. Content:- Introduction Manufacturing Manufacturing flowchart IPQC test 2

3. Introduction Tablet is define as a compressed solid unit dosage form containing medicament with or without excipient. 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. 3

4. 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 4

5. 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 5

6. CONT…. 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 ◦C. Dried granules are screened through the appropriate mesh screen 6

7. CONT… 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 7

8. Method used in tablet formulation :- Tablet are commonly manufactured by Direct compression Dry granulation Wet granulation 8

9. 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. 9

10. Manufacturing flowchart 10

11. Dry granulation Dry granulation involve the compaction of the component of tablet formulation by mean of tablet press followed by milling and screening , prior to final compression into tablet. When initial blend of powder is forced into the dies of large capacity tablet press and is compacted by mean of flat-faced punches, the compacted masses are called as slugs, and process is called as “slugging”. The slugs are then screened or milled to produce granule . Granules are then compressed. 11

12. Manufacturing flowchart 12

13. Wet granulation Weight granulation process involve the wet massing of the powder, wet seizing or milling and drying. Wet granulation forms the granules by binding the powders together with an adhesive. Addition of granulating liquid to the powder involve the series of stages i.e. pendular, funicular, capillary, and droplet stage 13

14. Manufacturing flowchart 14

15. 15

16. Coating of tablet Tablet coating is a process where coating material applied to the surface of tablet to achieve desire properties of dosage form Objective To mask the test, odour, or colour of drug to provide physical and chemical protection to drug To control the release of drug from the tablet. 16

17. Coating excipient Film former Non enteric material – hydroxypropyl methyl cellulose, ethyl cellulose, methyl hydroxyethyl cellulose, ethyl cellulose, povidone, hydroxypropyl cellulose, polyethylene glycols. Enteric material – cellulose acetate phthalate, acrylate polymers, hydroxypropyl methyl cellulose phthalate, polyvinyl acetate phthalate. 17

18. Coating method Sugar coating Steps – 1)sealing, 2) sub coating, 3) syruping, 4) finishing and 5) polishing . Film coating Pan-pour method Pan-spray method 18

19. In process quality control test Official test Weight variation test Content uniformity test Disintegration test Dissolution test Unofficial test Hardness test Friability test 19

20. Weight variation test The U.S.P. weight variation test is run by weighing 20 tablets individually, calculating the average weight, and comparing the individual tablet weights to the average. The tablets meet the USP test if “ Not more than 2 tablets are outside the percentage limit and if No tablet differs by more than 2 times the percentage limit.” 20 Average weight of tablets (mg) Maximum percentage difference allowed 130 or less ±10 130 to 324 ±7.5 More than 324 ±5

21. Content uniformity test In this test 30 tablets are randomly selected for sample, and at least 10 of them are assayed individually according to the official assay method. Nine of the 10 tablets must have potency within ± 15 % of the labeled drug content. Only one tablet may be within ± 25%. If this conditions are not met then the tablets remaining from the 30 must be assayed individually and none may fall outside ± 15% of the labeled content. Conclusion: Out of the 30 tablets the potency of only 2 tablets may remain within ± 15 to ± 25 % rest of all the tablets should remain within ± 15%. 21

22. Disintegration test For most tablets, the first important step toward solution is breakdown of the tablet into smaller particles or granules – this process is known as disintegration. The time a tablet takes to disintegrate is the disintegration time. The USP device to test disintegration uses glass tubes with the following dimensions: Number of tubes = 6 Length = 3 inches Upper end open, lower end closed with #10 mesh screen 22

23. To test the disintegration time one tablet is placed in each tube, and the basket rack assembly is positioned in a 1-litre beaker of water, simulated gastric fluid or simulated intestinal fluid, at 37◦C ± 2◦C, such that the tablet remain 2.5 cm from the bottom of the beaker. A standard motor moves the basket up and down through a distance of 5 to 6 cm at a frequency of 28 to 32 cpm (cycles per minute). USP disintegration test will be passed if all the tablets disintegrate and the particles passed through the #10 mesh screen within the specified time. 23

24. 24 Majority of the uncoated tablets have maximum disintegration time (DT) of 30 minutes, Enteric coated tablets shows no evidence of disintegration after 2 hrs. in simulated gastric fluid. The same tablets are then tested in simulated intestinal fluid and are to disintegrate in 1 hrs. Dissolution test Disintegration test simply identifies the time required for the tablet to break up under the condition of the test but it does not ensure the drug release in the bulk of the fluid. Rate of dissolution is directly related to the efficacy of the drug. In general, a single tablet is placed in a small wire mesh basket and immersed in the dissolution medium contained in a 1000 ml flask at 37 ◦ ± 0.5 ◦ C. Generally it is rotated at 50 rpm and time require for dissolution is noted.

25. Hardness test The hardness is pressure at which the tablet crushes . Unit of hardness: Kg/sq.in. Or lb./ sq.in Limit: Generally maximum 5 kg/sq.in. Hardness is required . Hardness tester: Monsanto tester, strong-cobb tester, Pfizer tester, erweka tester, etc. Friability test Tablet hardness is not an absolute indicator of strength since some formulations, when compressed into very hard tablets may produce chipping, capping and lamination problems. Therefore another measure of tablet strength i.e. friability is often measured, i.e. the friability. 25

26. Instrument: ROCHE FRIABILATOR Method: Few tablets, previously weighed (W1) are taken in the plastic chamber of the laboratory friability tester. In the plastic chamber the tablets are subjected to abrasion and shock by rotating the plastic chamber at 25 rpm for 4 mins (i.e. total 100 revolutions). The tablets are dusted and reweighed (W2) . Limit For conventional compressed tablet the weight loss should be within 0.5 to 1.0 %. 26 Friability = 100×(1-w2/w1)

27. Reference 27 Roop k Khar, SP Vyas, Farhan k Jain. Lachman/Liberman's the theory and practice of industrial pharmacy . CBS publisher& distributor pvt ltd, 2013. Michael E. Aulton, K. M. (n.d.). Aulton's pharmaceutics the design and manufacture of medicines. Churchill Livingstone Elsevier . Indian Pharmacopoeia Commission. Indian Pharmacopoeia. 7 th ed. Ghaziabad: Indian Pharmacopoeia Commission : 2014.
United States Pharmacopeial Convention. United Stated Pharmacopoeia 33- National Formulary 28. USA : Stationary office; 2010.