Technology of Making Tablets

1. Technology of Making Tablets Murat Kizaibek

2. Tablets are solid dosage forms consisting of active ingredient(s) and suitable pharmaceutical excipients. They may vary in size, shape, weight, hardness, thickness, disintegration and dissolution characteristics, and in other aspects. They may be classyfied, according to the method of manufacture, as compressed tablets or molded tablets.

3. Advantages • Production aspect • Large scale production at lowest cost • Easiest and cheapest to package and ship • High stability • User aspect (doctor, pharmacist, patient) • Easy to handling • Lightest and most compact • Greatest dose precision & least content variability

4. Disadvantages • Some drugs resist compression into dense compacts • Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or impossible to formulate and manufacture as a tablet that provide adequate or full drug bioavailability • Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating

5. Types of tablets • 1)compressed tablets • 2)sugar coated tablets • 3)film coated tablets • 4)enteric coated tablets • 5)effervescent tablets • 6)chewable tablets • 7)dispersible tablets • 8)sustained release tablets

6. 9)multilayer tablets • 10)sublingual tablets • 11)toroches • 12)buccal tablets • 13)implant tablets • 14)hypodermic tablets • 15)solution tabletc • 16)vaginal tablets

7. EXCIPIENTS FOR COMPRESSED TABLETS Compressed tablets usually contain a number of pharmaceutical adjuncts, known as excipients, in addition to the medicinal substance. The use of appropriate excipients is important in the development of the optimum tablets. Excipients determine the bulk of the final product in dosage forms such as tablet, capsule, etc., the speed of disintegration, rate of dissolution,release of drug, protection against moisture, stability during storage, and compatibility . Excipients should have no bioactivity, no reaction with the drug substance, no effect on the functions of other excipients, and no support of microbiological growth in the product .

8. A. DILUENTS Diluents increase the volume to a formulation to prepare tablets of the desired size. Widely used fillers are lactose, dextrin, microcrystalline cellu-lose starch, pregelatinized starch, powdered sucrose, and calcium phosphate.

9. The diluent is selected based on various factors, such as the experience of the manufacturer in the preparation of other tablets, its cost, and compatibility with other formulation ingredients. For example, in the preparation of tablets or capsules of tetracycline antibiotics, a calcium salt should not be used as a diluent since calcium interferes with absorption of the antibiotics from the GI tract.

10. B.BINDERS • Binders promote the adhesion of particles of the formulation. Such adhesion enables preparation of granules and maintains the integrity of the final tablet. As listed in the Table, Commonly used binding agents include: starch, gelatin and sugars (sucrose, glucose, dextrose, and lactose).

11. Examples of Binders

12. C. LUBRICANTS • Lubricant is a substance capable of reducing or preventing friction, heat, and wear when introduced as a film between solid surfaces. It works by coating on the surface of particles, and thus preventing adhesion of the tablet material to the dies and punches. Glycerylmonostearate(USP/NFCH2(OH)CH(OH)CH2O2CC17H35) is one example of a lubricant. Lubricants play more than one role in the preparation of tablets as described below.

13. 1. Lubricants improve the flow of granules in the hopper to the die cavity. • 2. Lubricants prevent sticking of tablet formulation to the punches and dies during formulation. • 3. Lubricants reduce the friction between the tablet and the die wall during the tablet’s ejection from the tablet machine. • 4. Lubricants give a sheen to the finished tablets.

14. Commonly used lubricants include: talc, magnesium stearat, calcium stearate ,stearic acid, hydrogenated vegetable oils and (PEG).

15. D. DISINTEGRATORS • The breakup of the tablets to smaller particles is important for dissolution of the drug and subsequent bioavailability. Disintegrators promote such breakup. To rupture or breakup of tablets, disintegrating agents must swell or expand on exposure to aqueous solution. Thus, the most effective disintegrating agents in most tablet systems are those with the highest wa-ter uptake property. In general, the more hydrophilic, the better disinte-grating agents are therefore highly hydrophilic. A list of typical disinte-grants is tabulated in Table

17. E. WETTING AGENTS • Water molecules attract each other equally in all directions. Water molecules on the surface, however, can only be pulled into the bulk water by water molecules underneath, since there are no water molecules to pull in the opposite direction. The surface tension of water is strong enough to support the weight of tiny insects such as water striders. The surface ten-sion in action can be visualized by placing a small drop of alcohol on a thin layer of water. Alcohol with lower surface tension mixes with water causing reduction in the surface tension in the local region. Owing to the higher surface tension of water in the neighbor, water is pulled from the alcohol dropped region into the neighbor, and this leads to the formation of a dry spot in the middle of the water layer.

18. wet granulation: suitable for drugs that are stable to moisture and heat dry granulation: suitable for drugs that are sensitive to moisture and heat powder compression : suitable for drugs that are sensitive to moisture and heat, fill material possessing, good flowability and compressibility granulation direct compression Compressed tablet manufacture • The classification of manufacturing methods crystal compression：suitable for drugs with proper crystal form and good flowability

19. wet granulation adhesive drug smash sieving mix prilling excipients lubricant press mix dry processing granule

20. dry granulation adhesive drug smash sieving mix press cake smash processing granule excipient mix press

21. powder compression adhesive mix press drugs smash sieving mix excipients

22. crystal compression adhesive drugs smash sieving mix press mix excipients

23. wet granulation technology • (一)wet granulation methods and equipment: • 1.Extrusion grain methods and equipment: first prescription drug powder and the auxiliary materials mixed evenly to join adhesive soft material system, then with soft material compulsory extrusion way through has a certain size screen hole and granulating method.

24. wet granulation

25. weighing and blending the ingredients(disintegrant) preparing a damp mass screening the damp mass into pellets or granules drying the granulation sizing the granulation by dry screening adding lubricant and disintegrant, and blending tableting by compression Compressed tablet manufacture—— wet granulation • The steps of wet granulation (liquid binder) Internal(内加法) External(外加法)

26. The classification of tablet presses • Tablet presses: a. single-punch presses b. multi-station rotary presses

27. The main components of single-punch tablet presses Core components: die lower punch upper punch

28. The basic mechanical process of tableting with single-punch presses a) filling material b) scraping away the excessive granulation c) forming a tablet by compression d) pushing up the tablet to stage surface e) shoving the tablet aside

29. A picture of multi-station rotary press hopper feed-frame head: upper turret, lower turret, die table upper turret die table lower turret

31. A: upper punch B: die cavity C: die D: lower punch The core components and compression cycle of rotary presses The compression is applied by both the upper punch and the lower punch. The compression cycle of a rotary tablet press

33. Compressed tablet manufacture—— Direct compression tableting Suitable for 1) granular chemicals possessing free flowing and cohesive properties e.g. potassium chloride 2) chemicals added with special pharmaceutical excipients which impart the necessary qualities for the production of tablets by direct compression

34. The direct compression tableting excipients include: a) fillers, as spray-dried lactose, microcrystals of alphamonohydrate lactose, sucroseinvert ,sugar – corn starch mixtures, microcrystalline cellulose, crystalline malt and dicalcium phosphate; d) disintegrants, as direct-compression starch, sodium carboxymethyl starch, cross-linked carboxymethylcellulose fiber, and cross-linked polyvinylpyrrolidone; c) lubricants, as magnesium stearate and talc; d) glidants, fumed silicon dioxide

35. Sophora Alopecuruldes L．Seed Tablet optimization

36. excipient prilling 、 processing granule mix mix powder of sophora AIopecuroides L． Seed 制软材 press 1％Magnesium stearate

37. table 1 the influence of different adhesive to Tablet hardness

38. table 2 the influence of different fillers to Tablet hardness

39. table 3 factor level

40. A×B Result Total Test NO. 　　A 　　B Ⅰ Ⅱ 1 2 table 4 Result of Orthogonal test 1 2 3 1 2 3 1 2 3 23.0 21.8 21.6 1 2 3 2 3 1 3 1 2 21.4 22.5 22.5 1 2 3 3 1 2 2 3 1 22.2 22.0 22.2 1 2 3 4 5 6 7 8 9 K1 K2 K3 1 1 1 2 2 2 3 3 3 17.8 24.2 24.4 3.1 2.9 6.0 2.8 3.1 5.9 3.2 2.7 5.9 4.1 4.4 8.5 4.0 4.1 8.1 4.2 3.4 8.5 4.0 3.8 7.8 3.9 4.2 8.1 1.1 0.2 0.6 R×6 6.6 1.4

41. table5 Analysis of variance table

42. table６　微晶纤维素用量影响苦豆子片硬度的ｑ检验（ｎ＝６）table６　微晶纤维素用量影响苦豆子片硬度的ｑ检验（ｎ＝６） ｑ界值

43. Tablet coating The reasons for tablet coating 1) to protect the medicinal agent against destructive exposure to air and/or humidity; 2) to mask the taste of the drug; 3) to provide special characteristics of drug release; 4) to provide aesthetics or distinction to the product; 5) to prevent inadvertent contact by nonpatients with the drug substance

44. The general methods involved in coating tablets are as follows 1) sugarcoating tablets 2) film-coating tablets 3) enteric coating 4) pan coating 5) fluid-bed or air suspension coating 6) compression coating

45. The sugarcoating of tablets may be divided into the following steps: 1) waterproofing and sealing (if needed) 2) subcoating 3) smoothing and final rounding 4) finishing and coloring (if desired) 5) polishing

46. 片芯 ——包层隔离——包粉衣层——包糖衣层——包有色糖衣层——打光

47. film-coating machine

50. 1) waterproofing and sealing (if needed) aim: to prevent the components from being adversely affected by moisture; one or more coats; shellac , zein , or a polymer as cellulose acetate phthalate 2) Subcoating aim: to bond the sugar coating to the tablet and provide rounding a) 3 to 5 subcoats of a sugar-based syrup are applied. The sucrose and water syrup also contains gelatin, acacia, or PVP.