Tablet - A complete information

this presentation slide has been prepared to add valuable information about tablet (solid dosage form). I hope that it will surely help the pharma aspirants for their examination.

1. TABLET P repared By Guided By VAIBHAV TRIPATHI Dr . Deepak K. Dash (Asst. Prof.) (Principal) Royal College of Pharmacy, Raipur (C.G.)

2. Index Ideal properties Advantages/ Disadvantages C lassification of Tablets Excipients Granulation Techniques Equipments Tablet Tooling Processing Problems

3. Tablet Tablets are compressed solid unit dosage form containing medicament with/ without excipients.

4. Ideal properties Must be sturdy enough to withstand shock during PSD Must be able to release API at desirable time and rate Must be physico - chemically stable to maintain physical & chemical integrity of API till expiry date.

5. Ideal properties Must be free from any sort of defects. Must be uniform in wt. Must retain all attributes in p rescribed manner for its stability

6. Advantages Easy to administered. Easy to dispense. More stable. Accuracy in dose. Bitter and nauseous substance can be easily dispensed. Light and compact. Economical . Sustained release product is possible by enteric coating.

7. Disadvantages Problem with compression to crystalline drug. Hygroscopic drugs are not suitable for compressed tablets. Drugs with low or poor water solubility, slow dissolution , may be difficult to formulate . Cost of production may be increase because of coating and encapsulation to remove bitter and unpleasant taste. Swallowing is difficult especially for children and ill (unconscious) patients.

8. Types TABLETS INGESTED ORALLY ORAL CAVITY TABLETS TABLETS ADMINISTERED BY OTHER ROUTE TABLETS USED TO PREPARE SOLUTIONS TABLET TRITURATES

9. Types TABLETS INGESTED ORALLY 1 . Compressed tablet 2. Multiple compressed tablet 3. Sustained action tablet 4. Multilayered 5. Enteric coated 6. Sugar coated 7. Chewable

10. Types 2. ORAL CAVITY TABLETS Buccal tab. Sublingual Lozenges Dental cones

11. Types 3. Tablets for other routes Implantation Vaginal 4. Tablets for solution Effervescent

12. Types 5. Tablet triturates Dispensing Hypodermic

13. Excipients Excipients/ additives are mixed with API to fabricate tablet dosage form Additives are selected to explore intended effect in tablet. Provide proper wt. and vol. to the tablet Alter solubility BvB modifier Improve patient compliance Drug release modification Helps in product identification

14. Excipients Diluent Binder / Adhesive Disintegrants Lubricant/ Glidant Coloring Agent Flavoring Agent S weetening Agent

15. Excipients Diluent to increase the bulk vol. to permit use of direct compression manufacturing Lactose, starch, Dibasic calcium phosphate dehydrate Calcium sulphate dihydrate , Mannitol Sorbitol, Sucrose , Dextrose

16. Excipients Binder provides strength to the granules Acacia, tragacanth - Solution for 10-25% Conc. Cellulose derivatives- Methyl cellulose, Hydroxy propyl methyl cellulose, Hydroxy propyl cellulose Gelatin- 10-20% solution Glucose- 50% solution Polyvinylpyrrolidone (PVP)- 2% conc. Starch paste-10-20% solution Sodium alginate Sorbitol

17. Excipients Disintegrants to facilitate breaking or disintegration in the GIT . One part is mixed with other excipients before granules formation and the other is mixed with the dry granules before compression. Starch- 5-20% of tablet weight . Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose ) Alginate

18. Excipients Lubricant / Glidant to prevent adhesion of the tablet materials to the surface of dies and punches , reduce inter particle friction improve the rate of flow of the tablet granulation by reducing the friction between the particles. Stearic acid, Stearic acid salt – Stearic acid , Magnesium stearate Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas such as Syloid , Aerosil in 0.25-3 % conc.

19. Excipients Coloring Agent All coloring agents must be approved and certified by FDA. Improve physical appearance Product Identification yellow 6-sunset yellow, yellow 5 Tartrazine , green 3- Fast Green,blue 1- Brilliant Blue ,blue 2 - Indigo carmine

20. Excipients Sweetening Agent For chewable tablet- flavor oil are used Saccharine (artificial): 500 time’s sweeter than sucrose Aspartame (artificial)

21. Excipients Flavoring Agent For chewable tablet- flavor oil are used Almond Oil, Benzaldehyde DL-Menthol , Ethyl Acetate Ethyl  Vanillin L-Menthol Methyl Salicylate Peppermint Oil

22. Granulation Process of size enlargement. Fine or coarse particles are transformed into larger aggregates. To improve flow property To prepare powder agglomerates To improve bulk density To prepare uniform size of aggregates To improve compaction To reduce the probability of capping

23.   G ranulation  

24. Direct Compression Tablets are compressed directly from powder blend of API & suitable additives Without altering the physical features of the drug It means, no pretreatment (wetting or recompression) is required There is no need to prepare granules Potassium salt (chloride, bromide) ammonium chloride etc.

25. Direct Compression Advantages Economical - comparably fewer machines, less space, less time & less labor required Stability – better option for thermo labile & moisture sensitive APIs Improved dissolution rate- because tab. Disintegrate directly into API particles so as to comparatively faster dissolution Minimum machine related problems- less wear & tear Simple validation- due to fewer unit operations, easy to comply GMPs

26. Direct Compression Disadvantages Segregation - due to differences in density of the API & excipients. Cost – specially process excipients raise the cost of final product. BvB problem - poorly compressible APIs tend to release only 30 – 40 % active ingredient . It leads to designing large tab. Which may create difficult to swallow variation in functionality Lubricant sensitivity Re- workability

27. Dry Granulation The powder mixture is compacted in large pieces (slug) and subsequently broken down or sized into granules then final compression to produce tablet. Milling / Screening Pre- blending Slugging / roller compaction Dry screening Blending of lubricant Compression

28. Dry Granulation dies of large capacity tablet press and compacted using flat faced punches. compacted masses are called slugs and process is called slugging. Slugs milled or screened to produce good free flowing granules for compression.

29. Dry Granulation Advantages Good for moisture sensitive material Compatible for heat sensitive material Disadvantage Specialist equipment is required for granulation by roller compaction. Slugging and roller compaction lead to the generation of considerable dust . Does not permit uniform color distribution

30. Wet Granulation Wet granulation is a widely employed method for the production of compressed tablets. Weighing and blending the ingredients Preparing a dampened powder or a damp mass Screening the dampened powder or damp mass into pellets or granules Drying the granulation (oven) Sizing the granulation by dry screening Adding lubricant. Dry binder , colorant or Disintegrants may be also added in this step Forming tablets by compression

31. Wet Granulation Advantages To prevent segregation of the constituents of the powder blend. To improve flowability of the powder mixture. To improve the compaction characteristics of the powder mixture due to better distribution of the binder within the granules. To improve homogeneity and thus ensure content uniformity

32. Wet Granulation Advantages Useful technique for the manufacture of tablets containing low and or high concentrations of therapeutic agent Employs conventional excipients and therefore is not dependent on the inclusion of special grades of excipients

33. Wet Granulation Disadvantages Often several processing steps are required Solvents are required in the process which leads to a number of concerns : Drug degradation may occur in the presence of the solvent. The drug may be soluble in the granulation fluid. Heat is required to remove the solvent.

34. E quipments There are 3 main stages/ operations in tablet production Sizing Mixing Compression

35. E quipments 1. Sizing The sizing (size reduction, milling, crushing, grinding, pulverization) is an important step in the process of tablet manufacturing. A fine particle size is essential in case of excipients mixing with granules for its proper function . Fluid energy mill Colloidal mill Ball mill Cutting mill Roller mill Conical mill

36. E quipments 1. Sizing Fluid energy mill

37. E quipments 2 . Mixing Successful mixing of powder is very crucial to achieve uniform dose content in each and every compressed tablet. Each process of mixing has an optimum mixing time, and longer mixing may result in an undesired product. Blender's optimum mixing time and mixing speed must be evaluated during mixing. "V" blender Oblicone blender Container blender Tumbling blender Agitated powder blender

38. E quipments 2 . Mixing "V" blender

39. E quipments 3. Compression compression of powder for granulation Compression of granules into tablet compression of powder for granulation Compaction of powder by means of pressure roll. To prepare slug To produce directly compressible excipients Granulation of dry herbal drugs Eg . chilsonator

40. E quipments

41. E quipments 3. Compression compression of powder for granulation High Shear granulation: Little ford Lodgie granulator Little ford MGT granulator Diosna granulator Gral mixer

42. E quipments 3. Compression compression of powder for granulation Granulator with drying facility: Fluidized bed granulator Day nauta mixer processor Double cone or twin shell processor Topo granulator

43. E quipments 3. Compression Compression of granules into tablet Hopper for holding and feeding granules to be compressed Dies that define the size and shape of the tablet Punches for compressing the granules within the dies Cam tracks for guiding the movement of the punches Feeding mechanisms for moving granules from the hopper into the die Tablet ejector

44. E quipments 3. Compression Single punch machine The compression is applied by the upper punch making the single punch machine a “stamping press .”

45. E quipments 3. Compression B. Multi-station rotary presses The head of the tablet machine that holds the upper punches, dies and lower punches in place rotates As the head rotates, the punches are guided up and down by fixed cam tracks, which control the sequence of filling Then compression followed by ejection .

46. E quipments 3. Compression B. Multi-station rotary presses

47. E quipments 3. Compression B. Multi-station rotary presses The portions of the head that hold the upper and lower punches are called the upper and lower turrets The portion holding the dies is called the die table

48. T ablet Tooling Tooling means any industrial operation which is done with the help of a tool. U se of suitable tools for an industrial process Tablet tooling is a part/ set of machine Which consists of a die & upper- lower punches

49. T ablet Tooling

50. T ablet Tooling Name/ symbol/ design can be engraved into punch face to get the intended design on tablet. Tooling damage can be avoided by calculating the pressure of compressive load & the pressure at punch tips. The most common tools employed are refer as “BB TOOLING”.

51. T ablet Tooling 5.25 inches in length 0.75 inches barrel diameter 1 inch head diameter

52. T ablet Tooling Significance To ascertain shape & size of the tablet To fix identification mark on the tablet Proper tooling helps to meet many provisional requirements to comply with the protocols of GMPs like Dosage uniformity Optimum production efficiency Aesthetic appearance

53. Processing Problems An industrial pharmacist usually encounters number of problems during manufacturing. Such problems bring about defects in tablets Factors related to processing problems:- Formulation related Tableting process related Machine related

54. Processing Problems Capping Lamination Cracking Chipping Sticking Picking Binding Mottling Double Impression Wt. variation Black marks on tablets Delayed Disintegration

55. Processing Problems 1. Capping partial or complete removal of top or bottom portion of tablet . Reason Remedy Poorly finished dies Polish dies properly. Investigate other steels or other materials. Lower punch remains below the face of die during ejection. Make proper setting of lower punch during ejection. Damaged upper punch replace the tool Machine RPM too fast Speed adjustment

56. Processing Problems 2. Lamination Separation of a tablet into two or more distinct horizontal layers. Reason Remedy Air entrapment in granules improve granulation using tapered dies Rapid decompression Reduce turret speed and reduce the final compression pressure. Large amount of fines in the granulation Remove some or all fines through 100 to 200 mesh screen

57. Processing Problems 3 . Cracking Small, fine flaws observed on the upper and lower central surface of tablets Reason Remedy Tablet expands on ejection due to air entrapment. Use tapered die. Deep concavities cause cracking while removing tablets Use special take-off Tablets expand. Improve granulation. Add dry binders. Granulation too cold. Compress at room temperature.

58. Processing Problems 4. Chipping Breaking of tablet edges Reason Remedy Sticking on punch faces. Dry the granules properly or increase lubrication. Too much binding causes chipping at bottom. Optimize binding, or use dry binders. Groove of die worn at compression point. Polish to open end, reverse or replace the die. Concavity too deep to compress powder blend. Reduce concavity of punch faces. Use flat punches.

59. Processing Problems 5 . Sticking Tablet material adhering to the die wall Reason Remedy Granules not dried properly. Dry the granules properly. Make moisture analysis to determine limits. Too little or improper lubrication. Increase or change lubricant. Too little pressure. Increase pressure Compressing too fast. Reduce speed.

60. Processing Problems 6. Picking The material is removed or picked up by upper punch from the upper surface of the tablet. Reason Remedy Excessive moisture in granules. Dry properly the granules, determine optimum limit. Too much amount of binder. Reduce the amount of binder, change the type or use dry binders. Embossing or engraving letters on punch faces such as B, A, O, R, P, Q, G. Design lettering as large as possible. Plate the punch faces with chromium to produce a smooth and non-adherent face. Rough or scratched punch faces. Polish faces to high luster.

61. Processing Problems 7 . Binding Sticking of the tablet to the die and does not eject properly out of the die. Reason Remedy Too moist granules and extrudes around lower punch. Dry the granules properly. Insufficient or improper lubricant. Increase the amount of lubricant or use a more effective lubricant. Poorly finished dies. Polish the dies properly. Rough dies due to abrasion, corrosion. Investigate other steels or other materials or modify granulation.

62. Processing Problems 8. Mottling An unequal distribution of colour on the surface of a coloured tablet. Reason Remedy Migration of dye in the granules during drying. Drying the granules at low temperature. Use of different coloration of medicaments and excipients. Using the dye which can mask the colour of all medicaments.

63. Processing Problems 9. Double Impression If the upper punch is uncontrolled, it can rotate during the short travel to the final compression stage and create a double impression . Reason Remedy Free rotation of either upper punch or lower punch during ejection of a tablet. Newer presses have anti-turning devices, which prevent punch rotation.

64. Processing Problems 10. Weight Variation Weight variation occurs due to improper compression/ formulation of granules in a tablet machine Reason Remedy Granules are not in in uniform size. Provide uniform granules Restricted free flow of granules Add Glidant to improve flowability Variation in the speed of tablet machine. Calibrate machine speed Restricted hopper flow Adjust the hopper

65. Processing Problems 11. Black mark on tablets Unwanted mark on tablet due to presence of tiny particles Reason Remedy Granules having black particle Proper screening before compression Lubricant, grease or oil may contaminate the powder Inspect before using such materials Due to traces of any part of compression machine. Cleansing on daily basis can avoid this problem Manual error Check the material after each & every process

66. Processing Problems 12. Delayed disintegration When break down of tablets take more time than desired Reason Remedy Hard compression Optimize the compression pressure Over granulation Improve granulation Excessive blending time with lubricant Adjust the blending time

67. References Lachman L., Lieberman H.A., Theory And Practice of Industrial Pharmacy, (2009 ), Indian Edition, CBS Publication And Distributors , New Delhi. Hayes S. Remington: The Science and Practice of Pharmacy, volume I and volume II. Journal of the Medical Library Association. JMLA Tablets F. Indian Pharmacopoeia, 2010 Edition. Volume.;2: Tripathi DK, Industrial Pharmacy: A Comprehensive Approach, (2018), Pharma Med. Press/BSP Books, Andhra Pradesh . Kumar K.P. Sampath , A Text Book of Industrial Pharmacy (2019), Nirali Publication And Distributors, Maharashtra. https://www.slideshare.net/sanjay2043/tablet-processing-problems