Tablets: Introduction, ideal characteristics of tablets, classification of tablets. Excipients, preformulation and Formulation of tablets, granulation methods, compression and processing problems, Equipment's and tablet tooling.

Tablet is defined as a compressed solid unit dosage form containing medicaments with or without excipients.

According to the Indian Pharmacopoeia Pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drug or a mixture of drugs, with or without diluents
The advantages of the Tablet dosage form are:
Greatest dose precision and the least content variability.
Cost is lowest of all oral dosage form.
Lighter and compact.
Easiest and cheapest to package and strip.
Easy to swallowing with least tendency for hang-up.
Sustained release product is possible by enteric coating.
Objectionable odour and bitter taste can be masked by coating technique.
Suitable for large scale production.
Greatest chemical and microbial stability over all oral dosage form.
Product identification is easy and rapid requiring no additional steps when employing an embossed and/or monogrammed punch face.

1. Tablets Prepared By Mrs. Chaudhary J V SJVPM’s Rasiklal M. Dhariwal Pharmaceutical Education & Research , Chinchwad, Pune-19

2. 8/07/2024 Mrs.Chaudhari J V 2 UNIT-II Syllabus Tablets: Introduction, ideal characteristics of tablets, classification of tablets. Excipients, preformulation and Formulation of tablets, granulation methods, compression and processing problems, Equipments and tablet tooling . Tablet coating : Types of coating, coating materials, formulation of coating composition, methods of coating, equipment employed and defects in coating . Quality control tests: In process and finished product tests Liquid orals : Preformulation, Formulation and manufacturing consideration of syrups and elixirs suspensions and emulsions; Filling and packaging; evaluation of liquid orals official in pharmacopoeia

3. INTRODUCTION Tablet is defined as a compressed solid unit dosage form containing medicaments with or without excipients. According to the Indian Pharmacopoeia Pharmaceutical tablets are solid, flat or biconvex dishes, unit dosage form, prepared by compressing a drug or a mixture of drugs, with or without diluents 8/07/2024 Mrs.Chaudhari J V 3

4. The advantages of the Tablet dosage form are: Greatest dose precision and the least content variability. Cost is lowest of all oral dosage form. Lighter and compact. Easiest and cheapest to package and strip. Easy to swallowing with least tendency for hang-up. Sustained release product is possible by enteric coating. Objectionable odour and bitter taste can be masked by coating technique. Suitable for large scale production. Greatest chemical and microbial stability over all oral dosage form. Product identification is easy and rapid requiring no additional steps when employing an embossed and/or monogrammed punch face. 8/07/2024 Mrs.Chaudhari J V 4

5. Disadvantages of Tablet dosage form are : Difficult to swallow in case of children and unconscious patients. Some drugs resist compression into dense compacts, owing to amorphous nature, low density character. Drugs with poor wetting, slow dissolution properties, optimum absorption high in GIT may be difficult to formulate or manufacture as a tablet that will still provide adequate or full drug bioavailability. Bitter testing drugs, drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating. In such cases, capsule may offer the best and lowest cost. 8/07/2024 Mrs.Chaudhari J V 5

6. 8/07/2024 Mrs.Chaudhari J V 6 Ideal characteristics of tablets A tablet should have elegant product identity while free of defects like chips, cracks, discoloration, and contamination. Should have sufficient strength to withstand mechanical shock during its production packaging, shipping and dispensing. Should have the chemical and physical stability to maintain its physical attributes over time The tablet must be able to release the medicinal agents in a predictable and reproducible manner. Must have a chemical and microbial stability over time so as not to follow alteration of the medicinal agents.

7. CLASSIFICATION OF TABLETS Tablets ingested orally 1 . Compressed tablet 2.Multiple compressed tablet 3.Multilayered tablet 4. Sustained action tablet 5. Enteric coated tablet 6. Sugar coated tablet 7. Film coated tablet 8. Chewable tablet B. Tablets used in oral cavity 1.Buccal tablets 2. Sublingual tablets 3. Lozenges 4.Dental cone s C. Tablets administered by other route Implantation tablet Vaginal tablet Rectal Tablet Hypodermic Tablet D. Tablets used to prepare solution Effervescent tablets Dispensing tablets Tablet triturates Hypodermic Tablet 8/07/2024 Mrs.Chaudhari J V 7

8. Different types of Tablets (A) Tablets ingested orally: 1. Compressed tablet, e.g. Paracetamol tablet 2. Multiple compressed tablet 3. Repeat action tablet 4. Delayed release tablet, e.g. Enteric coated Bisacodyl tablet 5. Sugar coated tablet, e.g. Multivitamin tablet 6. Film coated tablet, e.g. Metronidazole tablet 7. Chewable tablet, e.g. Antacid tablet (B) 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 8/07/2024 Mrs.Chaudhari J V 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 ) 8/07/2024 Mrs.Chaudhari J V 9

10. COMPRESSED TABTET Meant For oral administration Disintegrate in water within 15 mins and dissolve drug as per monograph Exam. Paracetamol tablet

11. MULTIPLE COMPRESSED TABLET These tablets are prepared to separate physically or chemically incompatible ingredients or to produce repeated action or prolonged action products. The ingredients of the formulation except the incompatible material are compressed into a core tablet then incompatible substance along with necessary exciepient are compressed over previously compressed core

12. MULTILAYERED TABTETS Prepared by more than a single compression cycle Several different granules are compressed on top of other to form a single tablet composed of two or more layers Eg . Gluformin G2( Glimipiride and metformin )

13. SUSTAINED ACTION TABLETS Release drug slowly for sustained drug action Also called as controlled release, delayed release, prolonged release or time released dosage form After administration of tablet it provides the immediate release of some amount of drug that promptly produce the desired therapeutic effect and the remaining amount of drug is gradually or continuously released to maintain the level of drug over an extended period usually 12 to 24 hrs Eg : Voveran SR tablet 100 mg

14. ENTERIC COATED TABLETS Enteric coating resist disintegration and dissolution of tablet in the stomach but not in the intestine Enteric coating is employed for following reasons To prevent attack of gastric content (acid and enzymes) on drugs. To protect the stomach from irritant effect of certain drugs. Certain drugs have drug absorption more in intestine than stomach . Eg. Pantop (Pantoprazole-40 mg) tablet

15. SUGAR COATED TABLETS It is done to mask bitter and unpleasant taste and odour of the medicament It involves successive application of colored or uncolored sucrose based solution to tablet core Coating is water soluble and is quickly dissolved after swallowing It is done to improve palatability appeal of product. Disintegration time NMT 60 min. Eg . Fourtus B –Multivitamin sugar coated tablet

16. FILM COATED TABLET It involves the deposition of colored or uncolored thin film of polymer surrounding the tablet core. They protects the medicament from atmospheric effect. Advantage of film coating is durable, less bulky and less time consuming for coating operation Disintegration time NMT 30 min . Eg Voveran SR tablet.

17. CHEWABLE TABLETS These are compressed tablets designed to chew prior to swallow for the patient who have difficulty in swallowing Due to chewing disintegration time is reduced and the rate of absorption is increased. Mannitol is commonly used diluents which is directly compressible and has cooling sensation in the mouth Bad tasting drugs and drugs having high dose are difficult to formulate as chewable tablet Eg : Antacid - Gelucil plus : Dried aluminum hydroxide gel 250mg, magnesium hydroxide 200mg, activated dimethasone :

18. BUCCAL TABLETS Buccal tablets are generally flat or oval shaped which are placed in the buccal pouch where they disintegrates and dissolves the drug Absorption of drugs takes place through highly vascular mucosal lining of the mouth which moves the drug through buccal capillaries and enters general circulation from the oral venous system to the heart bypassing the stomach and liver without first pass metabolism Drug dose should not be more than 10-15 mg and should not have undesirable taste. Eg .: Tablets of ethisteron

19. SUBLINGUAL TABLETS These tablets are placed under the tongue where they dissolve or disintegrates quickly and are absorbed directly without passing into GIT Eg ISORDIL SUBLINGUAL: Isosorbide dinitrate 5mg .- Vasodilator

20. LOZENGES These are round, disc, oblong, triangular or rectangular shaped solid dosage form intended to be sucked The viscous liquid produced in the mouth retain medicament in contact with affected area for a long time Used for treatment of local infection of mouth and throat which slowly release the drug for systemic action They are prepared by moulding or compression method Eg Alex cough lozenge: Dexamethorphan HBR 5mg. Dry cough

21. DENTAL CONES Relatively minor compressed tablet which are meant for placing the tablet in empty sockets after tooth extraction Prevent bacterial growth in sockets by slowly releasing medicament in the socket and reduces bleeding by containing the astringent It contain excipient like lactose, sodium bicarbonate and sodium chloride They gets dissolved in 20 to 40 min.

22. IMPLANTATION TABLETS These are small, rod shaped or ovoid shaped sterile pellets composed of highly purified drug in rate controlling system. They are inserted into body tissue by surgical procedure. Drugs are release slowly over prolonged period of time, ranging from 3 to 6 months. Eg : Hormones like testosterone and deoxycorticosteron are implanted. used to treat alcohol use disorder and opioid dependence

23. VAGINAL TABLETS They are oval or pear shaped to facilitate retention in the vagina where tablet dissolve to release medicament Used in treatment of local infection and contraception Administered by means of a plastic tube inserter. Eg : Candid V6 : Clotrimazole 100mg. Fungicide.

24. EFFERVESCENT TABLETS Compressed tablet containing effervescent salts as additives which liberate carbon dioxide in presence of water. Carbon dioxide acts as effervescent and to mask unpleasant taste of medicament. Effervescence are produced due to chemical reaction between sodium bicarbonate, citric acid and tartaric acid Dissolve within 5 minutes. Eg : Histac -EVT :Ranitidine 150 mg: Hyperacidity.

25. DISPENSING TABLETS Disintegrates within 3 minutes to produce uniform dispersion or solution. Shows faster action Contain superdisintegrants Eg Gastropen : Cisapride 5 mg : In constipation

26. HYPODERMIC TABLETS Compressed tablet containing one or more drug with water soluble ingredients Tablets are dissolved in sterile water or water for injection and administered by parental route. Not preferred nowadays because solution prepared may become nonsterile .

27. TABLET TRITURATES Small tablets ,usually cylindrical, moulded or compressed Content potent medicament with diluents Small scale prepared by hand operated tablet triturate moulds and on large scale automatic tablet triturates machine are used.

28. Tablet Ingredients In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients . Different excipients are: 1. Diluent 2. Binder and adhesive 3. Disintegrents 4. Lubricants and glidants 5. Colouring agents 6. Flavoring agents 7. Sweetening agents 8/07/2024 Mrs.Chaudhari J V 28

29. EXCIEPIENTS- functions Impart weight, accuracy, & volume(its allow acccuracy of dose) Improve solubility Increase stability Enhance bioavailability Modifying drug release Assist pdt identification Increase patient acceptability Facilitate dosage form design 8/07/2024 Mrs.Chaudhari J V 29

30. 1. Diluent : Diluents are fillers used to make required bulk of the tablet when the drug dosage itself is inadequate to produce the bulk. Secondary reason is to provide better tablet properties such as improve cohesion, to permit use of direct compression manufacturing or to promote flow. A diluent should have following properties: 1. They must be non toxic 2. They must be commercially available in acceptable grade 3. There cost must be low 4. They must be physiologically inert 5. They must be physically & chemically stable by themselves & in combination with the drugs. 6. They must be free from all microbial contamination. 7. They do not alter the bioavailability of drug. 8. They must be color compatible. 8/07/2024 Mrs.Chaudhari J V 30

31. Commonly used tablet diluents 1. Lactose-anhydrous and spray dried lactose 2. Directly compressed starch- Sta Rx 1500 3. Hydrolyzed starch- Emdex and Cellutab 4. Microcrystalline cellulose- Avicel (PH 101and PH 102) 5. Dibasic calcium phosphate dehydrate 6. Calcium sulphate dihydrate 7. Mannitol 8. Sorbitol 9. Sucrose- Sugartab, DiPac, Nutab 10. Dextrose 8/07/2024 Mrs.Chaudhari J V 31

32. 2. Binders and Adhesives: These materials are added either dry or in wet- form to form granules or to form cohesive compacts for directly compressed tablet. Example: 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 8/07/2024 Mrs.Chaudhari J V 32

33. 3. Disintegrants: Added to a tablet formulation to facilitate its breaking or disintegration when it contact in water in the GIT. Example: Starch- 5-20% of tablet weight. Starch derivative – Primogel and Explotab (1-8%) Clays- Veegum HV, bentonite 10% level in colored tablet only Cellulose Cellulose derivatives- Ac- Di-Sol (sodium carboxy methyl cellulose) Alginate PVP ( Polyvinylpyrrolidone ), cross-linked 8/07/2024 Mrs.Chaudhari J V 33

34. Superdisintegrants: Swells up to ten fold within 30 seconds when contact water. Example: Crosscarmellose - cross-linked cellulose, Crosspovidone - cross-linked povidone (polymer), Sodium starch glycolate - cross-linked starch. These cross-linked products swells with in 30 seconds when in contact with water. A portion of disintegrant is added before granulation and a portion before compression, which serve as glidants or lubricant. 8/07/2024 Mrs.Chaudhari J V 34

35. 4. Lubricant and Glidants : Lubricants are intended to prevent adhesion of the tablet materials to the surface of dies and punches, reduce inter particle friction and may improve the rate of flow of the tablet granulation. Glidants are intended to promote flow of granules or powder material by reducing the friction between the particles. Example: Lubricants- Stearic acid, Stearic acid salt - Stearic acid, Magnesium stearate, Talc, PEG (Polyethylene glycols), Surfactants Glidants - Corn Starch – 5-10% conc., Talc-5% conc., Silica derivative - Colloidal silicas such as Cab-O- Sil , Syloid , Aerosil in 0.25-3% conc. 8/07/2024 Mrs.Chaudhari J V 35

36. 5. Coloring agent: The use of colors and dyes in a tablet has three purposes: (1) Masking of off color drugs (2) Product Identification (3) Production of more elegant product All coloring agents must be approved and certified by FDA. Two forms of colors are used in tablet preparation – FD &C and D & C dyes. These dyes are applied as solution in the granulating agent or Lake form of these dyes. Lakes are dyes absorbed on hydrous oxide and employed as dry powder coloring. Example: FD & C yellow 6-sunset yellow,FD & C yellow 5- Tartrazine ,FD & C green 3- Fast Green,FD & C blue 1- Brilliant Blue ,FD & C blue 2 - Indigo carmine 8/07/2024 Mrs.Chaudhari J V 36

37. 6. Flavoring agents: For chewable tablet- flavor oil are used 7. Sweetening agents: For chewable tablets: Sugar, mannitol . Saccharine (artificial): 500 time’s sweeter than sucrose Disadvantage : Bitter aftertaste and carcinogenic Aspartame (artificial) Disadvantage: Lack of stability in presence of moisture. 8/07/2024 Mrs.Chaudhari J V 37

38. Tableting methods 8/07/2024 Mrs.Chaudhari J V 38 *

39. Powders intended for compression into tablets must possess two essential properties Powder fluidity or flowability The material can be transported through the hopper into the die To produce tablets of a consistent weight Powder flow can be improved mechanically by the use of vibrators, incorporate the glidant Powder compressibility The property of forming a stable, intact compact mass when pressure is applied is called powder compressibility Easily mixed with other particles Homogenous colouring etc Friction and adhesion properties 8/07/2024 Mrs.Chaudhari J V 39

40. Slugging (dry granulation) : Blend is forced into dies of large capacity tablet press and compacted using flat faced punches. compacted masses are called slugs and process is called slugging. c. Slugs milled or screened to produce good free flowing granules for compression. 8/07/2024 Mrs.Chaudhari J V 40

41. Dry compaction/Roller compaction 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. Materials of very low density require roller compaction to achieve a bulk density sufficient to allow encapsulation or compression. One of the best examples of this process is the densification of aluminum hydroxide. Roller compactor is capable of producing as much as 500 kg/hr of compacted ribbon like materials which can be then screened and milled in to granules for compression . 8/07/2024 Mrs.Chaudhari J V 41

42. Limitations of dry granulation 1- Dry granulation often produces a higher percentage of fines or non compacted products, which could compromise the quality or create yield problems for the tablet. 2- It requires drugs or excipients with cohesive properties. 8/07/2024 Mrs.Chaudhari J V 42

43. Wet granulation The most popular method (over 70% ) Granulation is done 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 Wet granulation is a process of using a solution binder to the powder mixture. The amount of liquid can be properly managed; overwetting = the granules to be too hard, underwetting = too soft and friable. Aqueous solutions are safer than other solvents. 8/07/2024 Mrs.Chaudhari J V 43

44. Procedure of Wet Granulation Step 1: Weighing and Blending Step 2: wet granulate prepared by adding the binder solution Step 3 : Screening the damp mass into pellets or granules (6-8mesh) Step 4 : Drying the granulation in thermostatically controlled ovens Step 5 : Dry screening: Step 6 : Mixing with other ingredients: A dry lubricant, antiadherent and glidant is added to the granules either by dusting over the spread-out granules or by blending with the granules. Dry binder, colorant or disintegrant may be also added in this step. Step 7 : Tableting : Last step in which the tablet is fed into the die cavity and then compressed. 8/07/2024 Mrs.Chaudhari J V 44

45. Limitations of wet granulation: 1- Multiple separate steps are involved. 2- Not suitable for heat and moisture sensitive drugs Equipments Traditionally, dry mixing in wet granulation process has been carried out using, Sigma blade mixer, Heavy-duty planetary mixer. 8/07/2024 Mrs.Chaudhari J V 45

46. List of equipments used in granulation High Shear granulation: i )Little ford Lodgie granulator ii)Little ford MGT granulator iii) Diosna granulator iv) Gral mixer Granulator with drying facility: i ) Fluidized bed granulator ii) Day nauta mixer processor iii) Double cone or twin shell processor iv) Topo granulator Special granulator : i ) Roto granulator ii) Marumerizer 8/07/2024 Mrs.Chaudhari J V 46

47. Compression Tableting procedure Filling Compression Ejection Tablet compression machines Hopper for holding and feeding granulation to be compressed Dies that define the size and shape of the tablet Punches for compressing the granulation within the dies Cam tracks for guiding the movement of the punches Feeding mechanisms for moving granulation from the hopper into the dies 8/07/2024 Mrs.Chaudhari J V 47

48. Single punch machine 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, compression and ejection. 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 8/07/2024 Mrs.Chaudhari J V 48

49. Compression cycle Granules from hopper empty in the feed frame (A) containing several interconnected compartments. These compartments spread the granulation over a wide area to provide time for the dies (B) to fill . The pull down cam (C) guides the lower punches to the bottom, allowing the dies to overfill The punches then pass over a weight-control cam (E), which reduces the fill in the dies to the desired amount A swipe off blade (D) at the end of the feed frame removes the excess granulation and directs it around the turret and back into the front of the feed frame The lower punches travel over the lower compression roll (F) while simultaneously the upper punches ride beneath the upper compression roll (G) 8/07/2024 Mrs.Chaudhari J V 49

50. The upper punches enter a fixed distance into the dies, while the lower punches are raised to squeeze and compact the granulation within the dies After the moment of compression, the upper punches are withdrawn as they follow the upper punch raising cam (H) The lower punches ride up the cam (I) which brings the tablets flush with or slightly above the surface of the dies The tablets strike a sweep off blade affixed to the front of the feed frame (A) and slide down a chute into a receptacle At the same time, the lower punches re-enter the pull down cam (C) and the cycle is repeated https:// www.pharmaguideline.com/2016/02/principle-of-tablet-compression-machine.html 8/07/2024 Mrs.Chaudhari J V 50

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53. The principle modification from earlier equipment has been an increase in production rate which is regulated by Number of tooling sets Number of compression stations Rotational speed of the press Multirotary machine High speed rotary machine 8/07/2024 Mrs.Chaudhari J V 53

54. PROCESSING PROBLEMS IN TABLET MANUFACTURING Tablet processing problems can be due to the imperfection in the formulation or in the compression equipment, or both of them. Thus we can classify the problems into following three types: 1 .   Excipient related problems:   chipping, picking, binding, sticking, mottling , 2 .   Process related problems :   capping, lamination, cracking 3 .   Machine related problem:   double impression . So at every step of the tablet manufacturing process, almost care should be taken to avoid defected tablet.

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56. CAPPING   Definition: Capping is a complete or partial separation of the upper or lower surface of the tablet horizontally from the main body of tablet, and comes off as a cap during ejection from the tablet press, or during subsequent handling. Reason: Capping is usually due to air entrapment in a compact during compression, and subsequent expansion of tablet on ejection of tablet from a die.

57. Sr. no Cause Remedy 1. Large number of fines in the material To remove the excess of fines the granulation material should bee passed through 100 to 200 mesh. 2. Too dry or very low moisture content(leading to loss of proper binding action) Moisten the granules suitably. Add hygroscopic substance eg ; sorbitol , methyl cellulose or PEG -4000 3 . Improperly dried granules Dry the granules properly. 4 . Inadequate or improper binder Increase the quantity of binder or use and appropriate one. 5 . Compression may not be firm due to cool temperature Compress the tablet material at higher temperature. 6 . Improper setting of the lower punch, which causes the sweep off blade to cut the surface Correct height of the lower punch should be adjusted so that the tablet is smoothly ejected out. 7. Deep concave punches or beveled edge face of punches Use flat punches

58. MOTTLING Definition: Mottling is uneven distribution of the colour on the surface of the tablet, with dark and light patches on it . Reason:  It is mainly due to coloured drug, whose colour differs from the colour of exciepients used for granulation of a tablet.

59. Sr. no Cause Remedy 1. A dye may cause mottling when it migrates to the surface during the granulation process The formulator is intended to change the solvent system, binder system, reduce drying temperature and use a smaller particle size.. 2. When coloured binder solution is not evenly distributed during mixing process Incorporate dry colour additive during powder blending step, then add fine powdered adhesive such as acacia and tragacanth and mix well and finally add granulating liquid. 3. Improperly mixed dye, especially during ‘Direct Compression’ Mix properly and reduce size if it is of a larger size to prevent segregation. 4 . A colored active ingredient used along with colourless excipients. Addition of appropriate colouring agent.

60. Picking: Definition:  Picking is the term used when a small amount of material from the tablets is sticking to the punch surface and gets removed from the tablet surface  This problem is more prevalent with the upper punch faces than on the lower ones. If this is left unchecked then this may lead to weight variation too. Reason :Picking is of particular concern when punch tips have engraving or embossing letters, as well as the granular material is improperly dried.

61. Sr. no Cause Remedy 1. Due to engraving or embossing letters on the upper punch faces such as B,A,O,R,P,Q,G. The letters to be embossed should be in large size particularly on small punches, or the size of the tablet be increased. 2. Rough or scratched punch surface The punch surface should be coated with chromium so as to get a smooth non adherent face of punch. 3. Too little or improper lubrication. Colloidal silica may be added in the formula as polishing agent to avoid sticking to the punch 4. Too deep dividing lines Reduce the depth and sharpness of the division. 5. Excess moisture in granules. Proper drying of granules and determine optimum limit. 6. Warm granules while compression Compress at room temperature and cool sufficiently before compression. 7. Excess binder. Reduce the amount or change the binder so that the adhesive force is reduced and more cohesive it becomes. 8. Low melting point medicament in high concentration Refrigerate granules and the entire tablet press.

62. STICKING Definition: Sticking refers to the tablet material adhering to the die walls. Due to this sticking with the die walls, additional force is required to eject the tablet form the die walls . Sticking also causes production of tablets with rough edges. Reasons: Improperly dried or improperly lubricated granules.   If this problem persists, then this can cause chipping of the tablet . It produced unusual stress on the cam track and punch heads resulting in their damage

63. Sr. no Cause Remedy 1. Low pressure Increase the pressure of punching 2. Fast compression Increase the contact time by reducing the speed 3. Greater concavity of the punch Reduce the concavity of the punch to optimum level. 4 Granules not dried properly Dry the granules properly. Make moisture analysis to determine limits 5. Too little or improper lubrication Increase or change lubricant. 6. Too much binder Reduce the amount of binder or use a different type of binder. 7. Hygroscopic granular material Modify granulation and compress under controlled humidity 8. Oily or waxy materials Modify mixing process and add an absorbent

64. CHIPPING Definition: Chipping is defined as the breaking of tablet edges while the tablet leaves the press or during subsequent handling and coating operations. Reason:  It is mainly due to improper machine setting, like ejection of the tablet.

65. Sr. no Cause Remedy 1. Too much drying Moisten the granule to plsticize with an hygroscopic substance 2. Worn out punches Polish the punch surface to get a smooth finish and reverse or replace the die. 3. Sticking of the tablet material to the punch Addition of proper lubricant and properly dry the granules. 4. Non cylindrical dies with gap in the edges Polish the dies so that they become cylindrical shape. 5. Barreled die(center of the die wider than ends) Polish the die to make it cylindrical. 6. Too much binding causes chipping at bottom Optimize binding or use dry binders.

66. Cracking Definition: Small, fine cracks observed on the upper and lower central surface of tablet, or very rarely on the sidewall are referred to as ‘Cracks’. Reason: It is observed as a result of rapid expansion of tablets, especially when deep concave punches are used.

67. Sr. no Cause Remedy 1. Large size of granules Reduce granule size. Add fines. 2. Too dry granules Moisten the granules properly and add proper amount of binder. 3 Tablet expand Improve granulation. Add dry binders. 4. Granulation too cold Compress at room temperature 5 Tablet expands on ejection due to air entrapment Use tapered die. 6 Deep concavities cause cracking while removing tablet Use special take-off. 8/07/2024 Mrs.Chaudhari J V 67

68. BINDING Definition:  Binding is sticking of the tablet to the die and does not eject properly out of the die . A film is formed in the die and ejection of tablet is hindered. With excessive binding, the tablet sides are cracked and it may crumble apart. Reasons:  It may be mainly due to lack of proper lubricant or less quantity of lubricant, or may be due to excess moisture in the tablet.

69. Sr. no Cause Remedy 1. Less or incorrect lubricant Increase the conc of lubricant or use appropriate lubricant 2. High moisture content of the tablet material The granules are to be properly dried. 3. Hard granules reducing the effectiveness of lubricant Reduce the size of the granules by passing through 30 mesh so that increased surface area can increase the chances of even binding of the lubricant. 4. Worn out dies walls Polish the dies properly 5. Excess pressure in the die Reduce the pressure with in the die.

70. Lamination Definition: Lamination is the separation of a tablet into two or more distinct horizontal layers. Reason: Air entrapment during compression and subsequent release on ejection. The condition is exaggerated by higher speed of turret .

71. Sr. No. Cause Remedy 1. Fast precompression of the tablet Precompression step should be included in the process, so that the pressure at the final compression is reduces. 2. Granules may contain oily or waxy material Modify mixing process. Suitable adsorbent or absorbent should be added. 4 Too much of hydrophobic lubricant e.g : Magnesium stearate Use a less amount of lubricant or change the type of lubricant 5 Rapid relaxation of the peripheral regions of a tablet, on ejection from a die Use tapered dies, i.e. upper part of the die bore has an outward taper of 3 to 5 8/07/2024 Mrs.Chaudhari J V 71

72. DOUBLE IMPRESSION Definition : Double Impression involves only those punches , which have engraving on them. Reason : During ejection process the lower punch travels a small distance down and then comes up to give a gentle push to the tablet, at this point when the lower punch moves down and comes up it moves in a swirling motion, due to the free rotation when it comes in contact with the tablet for the second time to push it up it leaves another impression on the tablet. Which leads to double impression. Remedy : Use keying in tooling, i.e. inset a key alongside of the punch, so that it fits the punch and prevents punch rotation. Newer presses have anti-turning devices, which prevent punch rotation

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74. COATING OF TABLETS Coating is a process of applying film of materials on the surface of pharmaceutical tablets to achieve special benefits like masking taste &/or odour, offer stability, sustain release of drug, etc. or Tablet coating is application of coating composition to a moving bed of tablets with the concurrent use of heated air to facilitate evaporation of solvent Reasons for coating: To mask the unpleasant taste and odor To improve the appearance of tablet To prevent the medicament from atmospheric effects To control the site of action of drugs( enteric coating) To produce the sustained released product. Methods of tablet coating : 1. Sugar coating: 2. Film coating 3. Enteric coating. https :// www.youtube.com/watch?v=1k7D0pJGTZI&list=RDCMUC0bXm7SnF_ssc47s6Ab8Yhg&index=1 8/07/2024 Mrs.Chaudhari J V 74

75. COATING OF TABLETS Methods for Tablet Coating: 1) Pan coating: 2) Fluidized bed coating: 3) Compress coating ● Pan coating: The tablets are placed in the pan. The speed of rotation is kept such that it keeps tablets separated from each other. The coating solution is poured or sprayed on the rotating tablet bed. Hot air is blown on the tablet bed & is exhausted viaduct. Its temperature & velocity should be neither too high to cause very fast drying of coating solution nor too low for the tablets to stick. After coating , polishing is done to impart shine to the tablets. 8/07/2024 Mrs.Chaudhari J V 75

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77. Process of tablet coating Pan Coating: Coating is done in a pan made up of copper or stainless steel Pan is rotated with the help of an electric motor Tablets are placed in pan and coating liquid is sprayed on tablet Hot air is blown in the pan. The speed of pan is adjusted in such a way that tablet remain separated from each other. After coating polishing is done in a polishing pan . 8/07/2024 Mrs.Chaudhari J V 77

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79. COATING OF TABLETS Fluidized bed coating: Process is an extension of fluidized bed dryer, where coating solution is spread on particles suspended in air ( called wurster technique) The tablets are suspended in the turbulent current of air in a chamber. Coating solution is atomized from different positions on the suspended tablets. The temperature of air is regulated to facilitate vaporization of solvent 8/07/2024 Mrs.Chaudhari J V 79

80. COATING OF TABLETS Press coating: ○ In this technique the granules of coating material are prepared and a layer of coating material is placed on the preformed tablet (below and above the tablet to be coated) ○ Post compression the granules of coating material evenly coat the preformed tablet . In this technique the granules of coating material are prepared and a layer of coating material is placed on the preformed tablet (below and above the tablet to be coated ) Post compression the granules of coating material evenly coat the preformed tablet. 8/07/2024 Mrs.Chaudhari J V 80

81. Press Coating 1.It is done in Drycota Rotary Tablet Machine automatically in a number of steps. 2. In this method tablets are compressed and layer of granules of coating material is placed on the tablet and compressed. 8/07/2024 Mrs.Chaudhari J V 81

82. The sugar coating of tablets process involves building up layers of coating materials on tablet cores by repetitively applying a coating solution or suspension and drying off the solvent. Sugar coating insulates and masks the color and texture of the core of the tablet . 1.Sieving 2. sealing 3.Sub coating 4. Syrup coating 5. Finishing 6. Polishing     Sugar coating 8/07/2024 Mrs.Chaudhari J V 82

83. i ) Sieving :- The tablets to be coated are shaken in a suitable sieve to remove the fine powder or broken pieces of tablets   ii) Sealing :-  Sealing is done to ensure that a thin layer of water proof material, such as , shellac or cellulose acetate phthalate is deposited on the surface of the tablets.  The shellac or cellulose acetate phthalate is dissolved in alcohol or acetone & its several coats are given in coating pan.  A coating pan is made up of copper or stainless steel.  The pan is rotated with the help of an electric motor. Examples of seal coating materials Zein   :- alcohol soluble protein derivative Ethyl cellulose Cellulose acetate Phthalate Polyvinyl acetate Phthalate HPMC ( hydroxypropyl methylcellulose) HPC ( hydroxypropyl cellulose )   Sugar coating 8/07/2024 Mrs.Chaudhari J V 83

84. iii) Sub coating :-  In sub coating several coats of sugar & other material such as Gelatin, Acacia etc. are given to round of tablet and to help in building up to tablet size.  Several coats of concentrated syrup containing acacia or gelatine are given.  After each addition of the syrup, dusting powder is sprinkled.  The dusting powder is a mixture of starch, talc & powdered acacia.   Sugar coating 8/07/2024 Mrs.Chaudhari J V 84

85. 8/07/2024 Mrs.Chaudhari J V 85 Ingredients %w/w Gelatin 2 to 10 Gum acacia 5 to 10 Sucrose powder 40 to 50 Distilled water upto 100 Ingredients %w/w Calcium carbonate 30 to 50 Titanium dioxide 2 to 10 Talc, asbestos-free 20 to 30 Sucrose (Powdered) 25 to 35 Gum acacia (Powdered) 1 to 5 Methods of sub-coating: Generally, 2 methods are used for sub-coating: Method 1:  Application of  gum(acacia/gelatin)  based solution followed by dusting with  powder (Talc/CaCO 3 )  and then drying. this step is repeated until the desired shape is achieved. Binder Solution involved in Method 1: An example of Ingredients involved in Method 1 is:

86. 8/07/2024 Mrs.Chaudhari J V 86 Ingredients %w/w Sucrose 30 to 50 Calcium carbonate 15 to 25 Talc (Asbestos free) 10 to 15 Gum acacia (Powdered) 1 to 5 Titanium dioxide 1 to 5 Distilled water 20 to 30 Methods of sub-coating: Method 2:  Application of a suspension of dry powder and gum/sucrose solution followed by drying. Examples of ingredients used for Method 2:

87. iv ) Syrup coating :-  This is done to give sugar coats, opacity & color to tablets  Several coats of the syrup are applied  Coloring materials & opacity agent are also added to the syrup  The process of coating is repeated until uniform colored tablets are obtained This process is specifically for smoothing and filing the irregularity/Roughness on the surface generated during sub-coating . It also increases the tablet dimension to a predetermined level. Smoothing usually can be accomplished by the application of a simple syrup solution of approximately 60 to 70% sugar solid. This syrup solution generally Contains pigments starch gelatin acacia or opacifier(TiO 2 ) if required. Sugar coating Opacifiers are additives that impart a rich, creamy, luxurious feel and appearance with ideal brightness . 8/07/2024 Mrs.Chaudhari J V 87

88. v) Finishing :-  Three to four coats of sugar are applied in rapid succession without dusting powder and cold air is circulated to dry each coat. Thus forms a hard smooth coat   vi) Polishing :-  Beeswax is dissolved in volatile organic solvent & a few coats of it are given, The finished tablets are transferred to a polishing pan is rotated at a suitable speed so the wax coated tablets are rubbed on the canvas cloth.  This gives a proper shining to the tablets Sugar coating Beeswax: 80 to 95% weight by weight Carnauba wax: 5 to 15% weight by weight 8/07/2024 Mrs.Chaudhari J V 88

89. 8/07/2024 Mrs.Chaudhari J V 89 Example of Sugar Coated Tablets: Example of sugar-coated tablets includes Vitamins, conjugated oestrogen , and mebeverine hydrochloride . Benefits of Sugar-Coated Tablets: The process requires low capital cost, and simple equipment, and is relatively easy to perform. It is cheap in terms of operating costs as the most typical ingredients used are water and sugar. It provides an attractive and glossy finish look and has wide consumer acceptability. Sugar-coated tablets are easy to take as orally because sugar coating masks the taste.

90. 8/07/2024 Mrs.Chaudhari J V 90 Disadvantages of Sugar Coating The achievement of high glossy quality often requires well-trained coating operators. The process is Labour intensive and requires a long processing time. Sugar-coated tablets are not cooperative with embossing, and the use of print for identification or labeling (the final gloss is achieved by a polishing step which can make imprinting difficult). Sugar coating increases the weight and size of the tablet (Increasing packaging and shipping costs) The Brittleness of the coatings causes the sugar-coated tablets exposed to potential damage if mishandled.

91. Reasons for film coating •To mask the disagreeable odor, colour or taste of the drug/tablet. • To offer a physical and/or chemical protection to the drug. • To protect drug from the deterioration effect of external environment. • Increasing the mechanical strength of the dosage form. • To improve the appearance of tablets   Film Coating. 1. Hydroxypropyl methyl cellulose. 2. Hydroxyethyl methyl cellulose. 3. Carbowax . 4. PEG-400 5. Ethyl cellulose   FILM COATING 8/07/2024 Mrs.Chaudhari J V 91

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93. Reasons for Enteric coating: 1. Medicament produce severe irritation in the stomach 2.The action of medicament is required in intestine 3.Medicament get decomposed or destroyed by the acidic medium of the stomach 4. Drug absorption is better in intestine 5. Delayed action effect is needed. Enteric coating: 1. Cellulose acetate phthalate. 2. Cellulose acetate trimellitate . 3. Cellulose acetate succinate . 4. HPMC acetate succinate . 5. HPMC phthalate. 6. Polymethacrylate .   ENTERIC COATING 8/07/2024 Mrs.Chaudhari J V 93

94. Reference The theory and practice of industrial pharmacy by Leon Lachman , A.lieberman 8/07/2024 Mrs.Chaudhari J V 94

95. THANK YOU 8/07/2024 Mrs.Chaudhari J V 95