Tablets formulation

TABLETS

1. TABLETS PRESENTED BY ARANTHA.J.JOSEPH. FIRST YEAR MPHARM PHARMACEUTICS St josephs college of pharmacy cherthala . 1

2. CONTENTS Introduction . Formulation. Design. Manufacturing. 2

3. TABLETS Tablets are solid preparations C onsisting of one or more active ingredient O btained by compressing uniform volumes of particles into various size and shape. 3

4. THE ADVANTAGES OF THE TABLET They are unit dosage Greatest dose precision and the least content variability. Cost is lowest of all oral dosage form. Lighter and compact. Easiest and cheapest to package. Easy to swallowing . Special release product is possible by enteric coating or delayed release product. 4

5. odour and bitter taste can be masked by coating technique. Suitable for large scale production. Greatest chemical ,mechanical and microbial stability over all oral dosage form. Product identification is easy and cheapest. 5

6. DISADVANTAGES OF TABLET Difficult to swallow in case of children and unconscious patients. Some drugs resist compression into dense compacts . Drugs with poor wetting , slow dissolution properties, is difficult to formulate. Bitter testing drugs , drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating . 6

7. DIFFERENT TYPES OF TABLETS (A) Tablets ingested orally: 1. Compressed tablet. e.g. Paracetamol tablet 2. Multiple compressed tablet. layered tablet. Compression coated tablets. 4. Delayed release tablet. e.g. Enteric coated Bisacodyl 5. Sugar coated tablet. e.g Multivitamin tablet 6. Film coated tablet. e.g. Metronidazole tablet 7. Chewable tablet. e.g. Antacid tablet 7

8. Tablets used in oral cavity 1. Buccal tablet e.g. Vitamin-c tablet 2. Sublingual tablet e.g. Vicks Menthol tablet 3. Troches or lozenges 4. Dental cone 8

9. (c) Tablets administered by other route: 1. Implantation tablet 2. Vaginal tablet, e.g. Clotrimazole tablet (D) Tablets used to prepare solution: 1. Effervescent tablet, e.g. Dispirin tablet (Aspirin) 2. Dispensing tablet, e.g. Enzyme tablet (Digiplex) 3. Hypodermic tablet 4. Tablet triturates e.g. Enzyme tablet (Digiplex) 9

10. TABLET GRANULATION Granulation : The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation . 10

11. Powders intended for compression into tablets must possess two essential properties. Powder fluidity or flowability Powder flow can be improved mechanically by the use of vibrators, glidant. Powder compressibility The property of forming a stable, intact compact mass when pressure is applied is called powder compressibility. 1 11

12. ADVANTAGES OF GRANNULATION To avoid powder segregation. To enhance the flow of powder. To produce uniform mixtures. To produce dust free formulations. To eliminate poor content uniformity. To improve compaction characteristics of mix. 12

13. Manufacturing of granules Dry granulation method wet granulation method Direct compression compression granulation. Wet granulation. 13

14. Dry granulation 14

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16. Direct compression Some Crystalline substances can compress directly. Directly compressible diluent is an Inert Compactable Maintain compression capacity even after adding disintegrates and other ingredients. Direct compression materials should posses Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate. 16

17. Drug Excipients Diluents Disintegrant Large sized tablets Slugs Granules Disintegrant Glidant Lubricant tablets Compression granulation 17 Weighing Mixing [blender] Slugging[tablet press, roller compactor. Screening sieve[20-25] Mixing Compression [tablet press]

18. 18 Important Steps Milling of drugs and excipients Mixing of ingredients Tablet compression

19. COMPRESSION GRANNULATION Dose of a drug is too high for its compression. Drug sensitive to heat and moisture. Aspirin, multi vitamins. Compaction of components of tablets by means of tablet press or machine. Milling and screening prior to fluid compression. 19

20. Roller compactor 20 On a large scale compression granulation can also be performed on a roller compactor . Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch .

21. It requires drugs or excipients with cohesive properties . Large particles must be used → ( acceptable flowability and bulk density ) If the drug powder has low compatability , it is difficult to form into tablets. Needs directly compressible filler that is usually expensive , e.g. microcrystalline cellulose (Avicel), spray dried lactose. LIMITATIONS OF DRY GRANULATION 21

22. WET GRANULATION It involves massing of a mix of dry Primary powder particles using a Granulating fluid. The fluid contain a solvent that must be Volatile and non-toxic e g water, Ethanol. The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying. 22

23. 23 • End point is tested by pressing a portion of the mass in the palm, if it crumbles (passed) under moderate pressure then, the mixture is ready for wet screening.

24. Advantages of wet granulation prevent segregation of the constituents of the powder blend . Improved cohesiveness and compressibility. To improve homogeneity . Uniform distribution of contents and colour . The dissolution rate of hydrophobic drugs may be improved by wet granulation method. 24

25. Limitations of wet granulation: Multiple separate steps are involved. Not suitable for heat and moisture sensitive drugs It is an expensive process- Cannot be used for moisture sensitive drugs. The use of soluble dyes often lead to migration of dyes during drying stage. Equipments Traditionally, dry mixing in wet granulation process has been carried out using, Sigma blade mixer, Heavy-duty planetary mixer. 25

26. Granulation mechanism To form grannules , bond must be formed between powder particles So they adhere Bond should be strong to prevent break down. 5 bonding mechanism Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild particles Formation of solid bridges after solvent evaporation. 26

27. Mechanism of granule formation Divided into 3 Nucleation Transition Ball growth 27

28. GRANULATION EQUIPMENTS 28 Single pot granulator. High shear mixture granulator. Fluid bed granulator.

29. 29 Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment . e.g. Single Pot Processor / One-Pot Processor

30. Single pot granulator 30

31. Rapid mixer granulator 31

32. High shear mixture granulation 32

33. 33 Short processing time. Lesser amount of liquid binders required . Highly cohesive material can be granulated. Increase in temperature may cause chemical degradation of thermolabile material. Over wetting of granules can lead to large size lumps formation. ADVANTAGES DISADVANTAGES

34. Fluid bed granulator 34 Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas. Granulating and drying can be completed in one step inside the machine.

35. 35 -Homogeneous granules . -- -G entle product handling. - - Uniform spraying of all particles in the fluid bed .

36. Advantages Reduces dust formation during processing reduces product loss. Improves worker safety. process suitable to: 􀂄 Potent compounds Minimizing product/operator Exposure Minimizing cross contamination. Reduced process time Reduced equipment and floor space requirements. DISADVANTAGES The Fluid Bed cleaning is labor-intensive and time consuming. Difficulty of assuring reproducibility . 36

37. Tablets Excipients 37

38. The common types of tablet’s excipients are described in the figure . 38

39. Diluent or filler Bulking agent. Increase size of the tablet. Suitable for handling. Most common fillers in tablets: 1. Lactose. 2. Sugar or sugar alcohol (glucose, sucrose, sorbitol and mannitol ). 3. Cellulose and microcrystalline cellulose. 4. diCalcium phosphate dihydrate. 39

40. Requirements for a good diluent Chemically inert, biocompatible, cheap. Non-hygroscopic. Good biopharmaceutical properties. water soluble or hydrophilic. compatibility Have an acceptable taste. 40

41. Disintegrants To ensure that the tablet, when in contact with a liquid , breaks up into small fragments , which promotes rapid drug dissolution . 41

42. Steps of the disintegration process First: The liquid wets the solid and penetrates the pores of the tablet. tablet breaks into smaller fragments ( aggregates of primary particles ). Second : The aggregates will deaggregate into their primary powder particles. 42

43. The Method of Disintegrant Addition Mixed with other ingredients prior to granulation & thus incorporated within the granules ( INTRAGRANULAR ADDITION ). Mixed with the dry granules.( EXTRA GRANULAR ADDITION ). Incorporated as both an intragranular and an extra granular portion . 43

44. Commonly Used Disintegrants 1 . Starch. 2.Cellulose (e.g. sodium carboxymethyl cellulose). Typical concentration of 1-5% by weight 3. High swelling disintegrants ( Modified Starch or Modified cellulose , in concentration of 1-2% 44

45. Binder 45 Ensure that granules and tablets can be formed with the required mechanical strength ( glue that holds powders together to form granules ). Eg- starch paste Glucose Gelatin solution Acacia Sucrose

46. Incorporation of binder 1. Dry Powder As dry powder mixed with other ingredient before wet granulation As a dry powder in dry granulation (roller compaction, slugging) 2. Solution binder As a solution in wet granulation. Binder can be added either dry with other excipients for granulation or Already dissolved in the granulating fluid ; water is the most common granulating fluid 46

47. Typical binder concentration is 2 – 10% by weight Binders can be: Insoluble in water , e.g. starch Soluble in water e.g. HPMC Soluble in water and ethanol e.g.Povidone 47

48. LUBRICANT Lubricants prevent adherence of granule/powder to die wall and to promote smooth ejection from the die after compaction. Mechanisms of Action : 1. Fluid lubrication. 2. Boundary lubrication . 48

49. 1. Fluid lubrication A layer of fluid is located between the moving surfaces separating them from each other & thus reduces the friction , e.g. liquid paraffin. 2. Boundary lubrication: The sliding surfaces are separated by only a very thin film of lubricant. So, the nature of the solid surfaces will therefore affect friction . 49

50. Disadvantages of lubricants 1. Lubricants tend to be hydrophobic . Under-lubricated blends tend to flow poorly and show compression sticking problems Over-lubricated blends can adversely affect tablet hardness and dissolution rate , as well as tablet strength . Eg : Magnesium Stearate Calcium Stearate , Talc Stearic Acid Sodium Lauryl Sulfate, liquid Paraffin , propylene glycol, (PG ) 50

51. Glidant or flow aid Improve flowability of the powder added during direct compaction and to granulation before tableting ( they reducing interparticulate friction ). Common Glidants are 1. Talc ( at concentration 1-2 % ). 2. Colloidal silica ( 0.2 % 51

52. Antiadherent Reduce adhesion between the powder and the punch faces & thus prevent particles sticking to the punches ; due to excess moisture or engraved and/or embossed punch face . Many lubricants, such as magnesium stearate , have also antiadherent properties. Also talc and starch can act as antiadherents . 52

53. S orbent Are substances that are capable of sorbing some quantities of fluids in an apparently dry state. Thus, oils or oil-drug solutions can be incorporated into a powder mixture which is granulated & compacted into tablets. e.g. Microcrystalline cellulose & silica . 53

54. F lavor Give the tablet a more pleasant taste or to mask an unpleasant one. Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat . They are often mixed with the granules as an alcohol solution. 54

55. Colourent It is added to tablets to aid identification and patient compliance. added during coating. It can also be added prior to compaction . ( can be added as an insoluble powder or dissolved in the granulation liquid. ) 55

56. S weeteners They are used in chewable tablet to exclude or limit the use of sugar in the tablets. Mannitol , 72% as sweet as sucrose. Saccharin, 500 times sweeter than sucrose . Disadvantage has a bitter taste after some time and carcinogenic . Aspartame , L argely replace saccharin . Disadv .: Lack of stability in the presence of moisture. 56

57. Tablet compression 57

58. Tablet Compression Machine Hopper for holding and feeding granules or powder to be compressed. Dies that define the size and shape of the tablet . Punches for compressing the granules within the dies . A feeding mechanism for moving granules from the hopper into the dies. 58

59. Tablet machine or tablet press 59

60. The compression cycle for a single punch tablet machine 60

61. Stages of Tablet Formation (Compaction Cycle) Gravitational flow of the powder from hopper via the die table into the die . (the die is closed at its lower end by the lower punch ). Tablet formation The upper punch descends , enters the die ,the powder is Compressed until a tablet is formed. After maximum applied force is reached,the upper punch leaves the powder. 61

62. Tablet ejection The lower punch rises until its tip reaches the level of the top of the die. The tablet is subsequently removed from the die and die table by a pushing device. 62

63. Tablet presses 63 Single punch. Rotary press. High speed rotary press. Multi layer rotary press.

64. Single Punch press (Eccentric Press): Bench-top models that make one tablet At a time (single-station presses) Disadvantages: production of small batches of tablets 64

65. Rotary Press( Multi station Press): ( 10 000 tablets per minute ) Large scale production. It consists of a number of dies and sets of punches ( from 3 up to 60). The dies are mounted in a circle in the die table both the die and the punches rotate together during operation of the machine. 65

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67. 67 The powder is held in a hopper whose lower opening is located just above the die table. The powder flows on to the die table & fed into the die by a feed frame . During powder compression both punches operate by vertical movement . After tablet ejection , the tablet is knocked away as the die passes the feed frame .

68. Reference Text book of physical pharmacy by Tripathi pg no 210-263. Sherwood BE & Becker JW (1998) “A new class of high-functionality excipients: silici-fied microcrystalline cellulose” Pharm Tech 22 78–88. Vogel, P.J.; Schmidt, P.C. Force –Time Curves of a Modern Rotary Tablet Machine. II. Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances. Drug Dev . Ind. Pharm. 1993, 19, 1917 . The theory and practice of industrial pharmacy fourth edition by lachman/lieberman page no 449-543 68

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