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Tablet Formulation Technology

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Tablets are solid dosage forms usually obtained by single or multiple compression of powders or granules. In certain cases tablets may be obtained by molding or extrusion techniques. They are uncoated or coated. Tablets are normally right circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be bevelled. They may have lines or break-marks (scoring), symbols or other markings.Tablets contain one or more active ingredients. They may contain excipients such as diluents, binders, disintegrating agents, glidants, lubricants, substances capable of modifying the behaviour of the dosage forms and the active ingredient(s) in the gastrointestinal tract, colouring matter authorized by the appropriate national or regional authority and flavouring substances. When such excipients are used it is necessary to ensure that they do not adversely affect the stability, dissolution rate, bioavailability, safety or efficacy of the active ingredient(s); there must be no incompatibility between any of the components of the dosage form.

Tablets are single-dose preparations intended for oral administration. Some are intended to be swallowed whole, some after being chewed and some after being crushed, some are intended to be dissolved or dispersed in water before being taken and some are intended to be retained in the mouth where the active ingredient(s) is/are liberated.

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Tablet Formulation Technology

  1. 1. Maksud Al- Hasan (Mahim)
  2. 2.  Tablet is defined as a compressed solid 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. 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. 3. Advantages of Tablet Dosage Form  Production aspect  Large scale production atLarge scale production at lowest costlowest cost  Easiest and cheapest toEasiest and cheapest to package and shippackage and ship  High stabilityHigh stability  User aspect (doctor, pharmacist, patient)  Easy to handlingEasy to handling  Lightest and most compactLightest and most compact  Greatest dose precision &Greatest dose precision & least content variabilityleast content variability
  4. 4. Disadvantages of Tablet  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.
  5. 5. 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
  6. 6. (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)
  7. 7. Tablet Ingredients In addition to active ingredients, tablet contains a number of inert materials known as additives or excipients. Different excipients are:  Diluent  Binder and adhesive  Disintegrents  Lubricants and glidants  Colouring agents  Flavoring agents  Sweetening agents
  8. 8. 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 .
  9. 9. EXCIEPIENTS- functions  Improve solubility  Increase stability  Impart weight, accuracy, & volume(its allow accuracy of dose)  Modifying drug release  Assist product identification  Increase patient acceptability  Facilitate dosage form design  Enhance bioavailability
  10. 10. 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.
  11. 11. Properties of Diluents 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.
  12. 12. 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).
  13. 13. Examples of Binders Carboxymethylcellulose, sodium Karaya gum Cellulose,microcrystalline(Avicel®) Starch, pregelatinized Ethylcellulose Tragacanth gum Hydroxypropyl methylcellulose Poly(acrylic acid) Methylcellulose Polypvinylpyrrolidone Acacia gum Gelatin Agar Dextrin Algin acid Glucose Guar gum Molasses
  14. 14. C. Disintegrates 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
  15. 15. D. 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)CH2O2 CC17H35) is one example of a lubricant. Lubricants play more than one role in the preparation of tablets as described below.
  16. 16.  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.
  17. 17.  Commonly used lubricants include: talc, magnesium stearat, calcium stearate ,stearic acid, hydrogenated vegetable oils and (PEG).
  18. 18. 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.
  19. 19. Compressed tablet manufacture •The classification of manufacturing methods 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 crystal compression : suitable for drugs with proper crystal form and good flowability
  20. 20. Tableting methods
  21. 21. drug excipients smash sieving mix adhesive prilling dry processing granule lubricant mix press wet granulation
  22. 22. dry granulation drug excipient smash sieving mix press cake smash processing granule adhesive mix press
  23. 23. drugs excipients smash sieving mix adhesive mix press powder compression
  24. 24. crystal compression drugs excipients smash sieving mix mix press adhesive
  25. 25. The steps of wet granulation (liquid binder) Internal External
  26. 26. The classification of tablet presses  Tablet presses: a. single-punch presses b. multi-station rotary presses
  27. 27. The main components of single-punch tablet presses Core components: • die • lower punch • upper punch
  28. 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. 29. A picture of multi-station rotary press hopper head: upper turret, lower turret, die table upper turret die table lower turret
  30. 30. The core components and compression cycle of rotary presses A: upper punch B: die cavity C: die D: lower punch The compression is applied by both the upper punch and the lower punch. The compression cycle of a rotary tablet press
  31. 31. 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
  32. 32. 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
  33. 33. Processing problems  Capping is the partial or complete separation of the top or bottom crowns of a tablet from the main body of the tablet.  Lamination is separation of a tablet into two or more distinct layers. Both of these problems usually result from air entrapment during processing.  Picking is removal of a tablet’s surface material by a punch.  Sticking is adhesion of tablet material to a die wall. These two problems result from excessive moisture or substances with low melting temperatures in the formulation
  34. 34.  Mottling is an unequal color distribution on a tablet, with light or dark areas standing on otherwise uniform surface. This results from use of a drug with a color different from that of the tablet excipients or from a drug with colored degradation products.  Weight variation-granule size distribution, poor fiow,punch variation  Hardness variation  Double impression-monograms or engraving on punch
  35. 35. 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
  36. 36. 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
  37. 37. 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
  38. 38. film-coating machine
  39. 39. 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.
  40. 40. b) When the tablets are partially dry they are sprinkled with a dusting powder, usually a mixture of powdered sugar and starch but sometimes talc, acacia, or precipitated chalk as well. c) Then drying the tablets. Repetition (15 to 18 times) the subcoating process until the tablets are of the desired shape and size.
  41. 41. 3) smoothing and final rounding aim: to complete the rounding and smooth the coatings 5 to 10 additional coatings of a thick syrup; This syrup is sucrose-based with or without additional components as starch and calcium carbonate. 4) finishing and coloring aim: to attain final smoothness and the appropriate color several coats of a thin syrup containing the desired colorant
  42. 42. 5) imprinting aim: to impart identification codes and other distinctive symbols to the product The imprint may be debossed, embossed, engraved, or printed on the surface with ink. 6) polishing aim: to render the tablets the desired sheen/gloss/luster a) pans lined with canvas cloth impregnated with carnauba waxand/or beeswax b) Pieces of wax may be placed in a polishing pan c) light-spraying of the tablets with wax dissolved in a nonaqueous solvent
  43. 43. Film-coating 1) The disadvantages of sugarcoating process a) time-consuming b) requiring the expertise of highly skilled technicians c) doubling the size and weight of the original uncoated tablets d) may vary in size from batch to batch and within a batch e) large tablets are not as easily swallowed as are small tablets.
  44. 44. 2) The advantages of film-coating process a) coated tablets having essentially the same weight, shape, and size as the originally compressed tablet b) The coating is thin enough to reveal any identifying monograms. c) far more resistant to destruction by abrasion than are sugar-coated tablets d) the coating may be colored to make the tablets attractive and distinctive.
  45. 45. 3) The components of nonaqueous film-coating solutions: a) film former: e.g. CAP b) alloying substance: to provide water solubility or permeability to the film e.g. PEG c) plasticizer: to render flexibility and elasticity to the coating e.g. castor oil d) surfactant: to enhance spreadability of the film e.g. polyoxyethylene sorbitan derivatives e) opaquants and colorants: e.g. titanium dioxide, FD&C or D&C dyes f) sweeteners, flavors, and aromas: saccharin, vanillin g) glossant: beeswax h) volatile solvent: alcohol-acetone mixture
  46. 46. 4) The components of a typical aqueous film-coating solutions: a) film-forming polymer (7-18%): e.g. cellulose ether polymers as HPMC, HPC and MC b) plasticizer (0.5-2.0%): e.g. glycerin, propylene glycol, PEG, diethyl phthalate, and dibutyl subacetate c) colorant and opacifier (2.5-8%): FD&C or D&C lakes and iron oxide pigments d) water
  47. 47. 5) Some problems with aqueous film-coating a) picking and peeling the appearance of small amounts or large amounts of film fragments flaking from the tablet surface b) orange peel effect roughness of the tablet surface due to failure of spray droplets to coalesce c) mottling an uneven distribution of color on the tablet surface d) bridging filling-in of the score-line or indented logo on the tablet by the film e) tablet erosion disfiguration of the core tablet
  48. 48. 5) Some problems with aqueous film-coating a) picking and peeling the appearance of small amounts or large amounts of film fragments flaking from the tablet surface b) orange peel effect roughness of the tablet surface due to failure of spray droplets to coalesce c) mottling an uneven distribution of color on the tablet surface d) bridging filling-in of the score-line or indented logo on the tablet by the film e) tablet erosion disfiguration of the core tablet
  49. 49. The reasons for capping, splitting or laminating of tablets 1) air entrapment 2) not immaculately cleaned or not perfectly smoothed punches 3) too great a proportion of fine powder 4) Tablets have aged or have been stored improperly
  50. 50. quality standards and compendial requirements The apparent physical features of compressed tablets: 1) shape: round, oblong, unique 2) thickness: thick or thin 3) diameter: large or small 4) flat or convex 5) unscored or scored in halves, thirds and quadrants 6) engraved or imprinted with an identifying symbol and/or code number 7) coated or uncoated 8)colored or uncolored 9) number of layer. The die and punches determine the physical features of compressed tablets.
  51. 51. quality standards and compendial requirements  Other physical specifications and quality standards: tablet weight weight variation content uniformity tablet thickness tablet hardness tablet disintegration drug dissolution  in-process controls  verification after the production
  52. 52. quality standards and compendial requirements —— tablet weight and Chp weight variation  Chp weight variation: sample amount 20 tablets  Tablets should comply with the following requirements stated in the table below. Average weight Weight variation limit Less than 0.3 g ± 7.5% 0.3 g or more ± 5%
  53. 53. quality standards and compendial requirements —— tablet weight and Chp weight variation The procedure of weight variation determination in Chp: Weigh accurately 20 tablets and calculate the average weight, then weigh individually each of the 20 tablets. Compare the weight of each tablet with the labelled tablet (if no labelled weight is stated, compare the weight of each tablet with the average weight calculated). No more than 2 of the individual weights exceed the weight variation limit stated in the table above and none doubles the limit.
  54. 54. quality standards and compendial requirements —— tablet hardness and friability Tablet hardness 1)The greater the pressure applied, the harder the tablets. 2) The hardness required by different tablets a) lozenges and buccal tablets: hard (dissolve slowly) b) the tablets for immediate drug release: soft 3) measurement a) special dedicated hardness testers b) multifunctional equipment
  55. 55. quality standards and compendial requirements —— content uniformity  applys to potent drug of low dose.  USP method, 10 tablets are individually assayed for their content. The amount of active ingredient in each tablet lies within the range of 85% to 115% of the label claim and the RSD is less than 6.0%.
  56. 56. quality standards and compendial requirements —— tablet hardness and friability Friability 1) It is used to determine a tablet’s durability 2) Method: allowing the tablets to roll and fall within the rotating apparatus (friabilator); determine the loss in weight; 3) requirement: weight loss ≤1%
  57. 57. Tablet Hardness Tester
  58. 58. Friability Tester
  59. 59. Dissolution Tester
  60. 60. Disintigration Tester
  61. 61. quality standards and compendial requirements —— tablet dissolution 1) The importance of in vitro dissolution test a) to guide the formulation and product development process toward product optimization b) to monitor the performance of manufacturing process c) to assure bioequivalence from batch to batch d) as a requirement for regulatory approval for product marketing for products registered with the FDA and regulatory agencies of other countries.
  62. 62. 2) The goal of in vitro dissolution is to provide a reasonable prediction of the product’s in vivo bioavailability. Basis: The combinations of a drug’s solubility and its intestinal permeability are supposed as a basis for predicting the likelihood of achieving a successful in vivo – in vitro correlation (IVIVC).
  63. 63. Considered are drugs determined to have: a) high solubility and high permeability (IVIVC may be expected.) b) low solubility and high permeability (IVIVC may be expected.) c) high solubility and low permeability d) low solubility and low permeability
  64. 64. 3) The formulation and manufacturing factors affecting the dissolution of a tablet a) the particle size of the drug substance b) the solubility and hygroscopicity of the formulation c) the type and concentration of the disintegrant, binder, and lubricant used d) the manufacturing method, particularly, the compactness of the granulation and the compression force e) the in-process variables
  65. 65. 4) Test method a) A volume of the dissolution medium is placed in the vessel and allowed to come to 37 ±0.5 .℃ ℃ b) The stirrer is rotate at the specified speed. c) At stated intervals, samples of the medium are withdrawn for chemical analysis 5) Requirement for rate of dissolution The specific required rates of dissolution are different for tablets containing different medicinal agents. e.g. not less than 85% of the labeled amount is dissolved in 30 minutes
  66. 66. 6) Inconsistencies in dissolution occur not between dosage units from the same production batch, but rather between batches or between products from different manufacturers. Pooled dissolution testing has emerged. This process recognizes the concept of batch characteristics and allows pooled specimens to be tested.
  67. 67. THANK YOU

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