Solid Dosage Forms

1. SALMAN BIN ABDULAZIZ UNIVERSITY COLLEGE OF PHARMACY TABLETS Solid Dosage Forms Dr. Mohammad Khalid Anwer e-mail:-mkanwer2002@yahoo.co.in

2. Tablets • Tablets defined as solid pharmaceutical dosage forms containing drug substances with or without suitable diluents and prepared by compression (large scale production) or molding methods (small scale operations).

3. It is probable that at least 90% of all drugs used to produce systemic effects are administered by the oral route. • Of drugs that are administered orally, solid oral dosage forms represent the preferred class of product. Tablets are the most commonly used solid dosage forms.

4. Advantages of solid dosage forms • Accurate dosage. • Easy shipping and handling. • Less shelf space needed per dose than for liquid. • No preservation requirements. • No taste masking problem. • Generally more stable than liquids, with longer expiration dates.

5. Advantages of Tablets • Precision and low content variability of the unit dose. • Low manufacturing cost. • The lightest and most compact, thus easy to package and ship. • Simple to identify by employing an embossed or monogrammed punch face.

6. Easy to swallow. • Appropriate for special-release forms. • Best suited to large-scale production. • Most stable of all oral dosage forms. • Essentially tamperproof.

7. In comparison to other oral dosage forms, tablets provide advantages to: • The pharmacist • In minimal storage space requirements • Ease of dispensing • The patient • In convenience of use, optimum portability, and lowest cost. • The physician • In flexibility of dosage (with bi­sected tablets), and in accuracy and precision of dosage in general.

8. Disadvantages of Tablets • Some drugs resist compression into dense compacts, owing to their amorphous nature or flocculent, low-density character. • Some drugs (e.g., those with an objectionable taste or odor, those sensitive to oxygen or atmospheric moisture) require encapsulation or entrapment before compression. These drugs are more appropriate in capsule form. • Some drugs with: • Poor wetting. • Slow dissolution properties. • Intermediate to large doses.

9. Characteristics of ideal tablets • It should be an elegant product having its own identity and Free of defects (e.g., chips, cracks, discoloration, contamination).

10. Strong enough to withstand the mechanical stresses of production packaging, shipping, and dispensing. • Chemically and physically stable over time. • Capable of releasing medicinal agents in a predictable and reproducible manner.

11. Tablet Types and Classes Tablets are classified according to their route of administration, drug delivery system, and form and method of manufacture.

12. Tablets for oral ingestion • Tablets for oral ingestion are designed to be swallowed intact, with the exception of chewable tablets.

13. (1) Compressed Tablets (CT) • Compressed tablets are formed by compression and have no special coating. • They are made from powdered, crystalline, or granular materials, alone or in combination with excipients such as binders, disintegrants, diluents, and colorants.

14. After compression, some compressed tablets may be coated with various materials. • Most compressed tablets are employed for the oral administration of drugs, but some may be used for the sublingual, buccal, or vaginal administration of drugs.

15. (2) Multiple Compressed Tablets (MCT) Multiple compressed tablets are layered or compression- coated. (a) Layered tablets are prepared by compressing a tablet granulation over a previously compressed granulation to form a two- or three-layered tablet, depending upon the number of separate fills. Generally each portion of fill is colored differently to prepare a multiple-colored as well as a multiple-layered tablet.

16. (b) Compression-coated, or dry-coated, tablets are prepared by feeding previously compressed tablets into a special tableting machine to compress an outer shell around the tablets. • This process applies a thinner, more uniform coating than sugar-coating, and it can be used safely with drugs that are sensitive to moisture. • This process can be used to: • Separate incompatible materials. • Produce repeat action or prolonged-action products.

17. (3) Repeat-action tablets: • Repeat-action tablets are layered or compression-coated tablets in which the outer layer or shell rapidly disintegrates in the stomach. The components of the inner layer or inner tablet are insoluble in gastric media, but soluble in intestinal media. • Example., Dexchlor tablets

18. (4) Delayed-action and Enteric-Coated Tablets (ECT) • These tablets delay the release of a drug from a dosage form. This delay is intended to: • Prevent destruction of the drug by gastric juices. • To prevent irritation of the stomach lining by the drug. • To promote absorption, this is better in the intestine than in the stomach. • Agents used to coat these tablets include fats, fatty acids, waxes, shellac, and cellulose acetate phthalate.

19. Enteric­ coated tablets are tablets with a coating that resists dissolution or disruption in the stomach but not in the intestines, thereby allowing for tablet transit through the stomach in favor of tablet disintegration and drug dissolution and absorption from the intestines. • e.g. Voltaren

20. (5) Sugar- and chocolate-Coated Tablets (SCT) The tablet that contains active ingredient(s) of unpleasant taste may be covered with sugar to make it more palatable. This type of tablet should be administered in whole form. Example: Vitaferro, Quinine.

21. (6) Film-Coated Tablets (FCT) The tablet is coated with a membrane of polymeric substances that improves physicochemical stability of the drug and delays the rate of drug absorption. e.g. Augmentin (7) Chewable tablets The tablets are placed in the mouth, chewed and swallowed. e.g. Talcid, Aspirin Direct

22. Tablets used in the oral cavity Tablets used in the oral cavity are allowed to dissolve in the mouth. (1) Sublingual tablets The tablet is placed under the tongue Sublingual tablets are absorbed quickly into the bloodstream e.g. Nitroglycerin, Uprima (2) Buccal tablets Buccal tablets are placed in the pouch between the cheek and gum They are usually small, flat and oval in shape e.g. Progesterone taqblet

23. (2) Troches, lozenges Troches (lozenges or pastilles) The tablets contain a drug substance in flavored base. Lozenges are allowed to dissolve in the mouth. They are commonly used for cold and sore throat. e.g. Chlorhexidine

24. Tablets used to prepare solutions • Tablets used to prepare solutions are dissolved in water before administration. (1) Effervescent tablets • Effervescent tablets are prepared by compressing granular effervescent salts or other materials (e.g., citric acid, tartaric acid, sodium bicarbonate) that release carbon dioxide gas when they come into contact with water to musk undesirable taste or to encourage rapid dissolution and absorption.

25. Tablet Ingredients (Formulation) • In addition to the active or therapeutic ingredient (s), tablets contain a number of inert materials. (additives or excipients) that have special functions.

27. Tablet excipients must meet certain criteria in the formulation: • Their cost must be low. • Nontoxic • Be commercially available • Be physiologically inert. • Must not be contraindicated by themselves (e.g., sucrose).

28. Physically and chemically stable by themselves and in combination with the drug(s) and other tablet components. • Free of any unacceptable microbiologic "load." • Be color-compatible (not produce any off-color appearance). • If the drug product is classified as a food, (certain vitamin products), the diluent and other excipients must be approved direct food additives. • Have no deleterious effect on the bioavailability of the drug(s) in the product.

29. (1)Diluents • Diluents are fillers designed to make up the required bulk of the tablet when the drug dosage amount is inadequate. • Diluents may improve cohesion, permit direct compression, or promote flow. • Common diluents include: kaolin, lactose, mannitol, starch, microcrystalline cellulose, powdered sugar, and calcium phosphate.

30. Selection of the diluent is based on: • the experience of the manufacturer • the cost of the diluent • its compatibility with the other ingredients. • For example, calcium salts cannot be used as fillers for tetracycline products because calcium interferes with the absorption of tetracycline from the gastrointestinal tract. • The dose of some drugs is sufficiently high that no filler is required (e.g., aspirin and certain antibiotics).

31. Lactose is the most widely used diluent in tablet • formulation. • but Lactosemay discolor in the presence of amine drug bases or salts of alkaline compounds. • Spray-dried lactose is one of several diluents now available for direct compression. • Microcrystalline cellulose, (Avicel), is a direct • compression material. • Two tablet grades exist: • PH 101 (powder). • PH 102 (granules).

32. (2) Binders and adhesives • Binders and adhesives are added in either dry or liquid form to promote granulation or to promote cohesive compacts during direct compression. • Common binding agents include: • 10%-20% aqueous preparation of corn­starch; • 25%-50% solution of glucose; molasses; • Various natural gums (e.g., acacia); (usually contaminated with bacteria) • Cellulose derivatives (e.g., methylcellulose, carboxymethylcellulose, microcrystalline cellulose); • Gelatins; and povidone.

33. (3) Disintegrants • Disintegrants are added to tablet formulations to facilitate disintegration when the tablet contacts water in the gastrointestinal tract. • Disintegrants function by drawing water into the tablet, swelling, and causing the tablet to burst. • Tablet disintegration may be critical to the subsequent dissolution of the drug and to satisfactory drug bioavailability.

34. Common disintegrants include: • Corn starch and potato starch; • Starch derivatives (sodium starch glycolate); • Cellulose derivatives (sodium carboxymethyl­ cellulose); • Clays (e.g., Veegum, bentonite); • A portion of disintegrantcan be added, with the lubricant, to the prepared granulation of the drug. This approach causes double disintegration of the tablet. • The tablet break into small pieces, or chunks. • The pieces of tablet break into fine particles.

35. (4) Lubricants, anti-adherents, and glidants • Lubricantsreduce the friction that occurs between the walls of the tablet and the walls of the die cavity when the tablet is ejected. Ex.: Talc, magnesium stearate, and calcium stearate. (b) Antiadherentsreduce sticking, or adhesion, of the tablet granulation or powder to the faces of the punches or the die walls. (c) Glidantspromote the flow of the tablet granulation or powder by reducing friction among particles.

36. (5) Colors and dyes • Colors and dyes provide product identification, and produce a more aesthetically appealing product. • The availability of natural vegetable colors is limited, and these colors are often unstable. • Two forms of color have typically been used in tablet preparation (FD&C and D&C dyes) which are applied as solutions. • Lakes are dyes that have been absorbed on a hydrous oxide. and used as dry powders.

37. (6) Flavoring agents • Flavoring agents are usually limited to chewable tablets or tablets that are intended to dissolve in the mouth. • Water-soluble flavors usually have poor stability. For this reason, flavor oils or dry powders are used. • Usually, the maximum amount of oil that can be added to a granulation without affecting its tablet characteristics is 0.5%-0.75%.

38. (7) Artificial sweeteners • Artificial sweeteners, like flavors, are typically used only with chewable tablets or tablets that are intended to dissolve in the mouth. • Some sweetness may come from the diluent (e.g., mannitol, lactose). Other agents (e.g., saccharin, aspartame) • Saccharin has an unpleasant aftertaste.

39. (8) Adsorbents • Adsorbents (e.g., magnesium oxide, magnesium carbonate, bentonite, silicon dioxide) hold quantities of fluid in an apparently dry state.

40. Methods of Tablet Preparation • The three basic methods for the preparation of compressed tablets are: • Wet granulation method. • Dry granulation method. • Direct compression.

42. The Wet Granulation Method • This method has more operational manipulations, and is more time-consuming than the other methods. • The wet granulation method is not suitable for drugs which are thermolabile or hydrolyzable by the presence of water in the liquid binder.

43. General steps involved in a wet granulation process are: • The powdered ingredients are weighed and mixed intimately by geometric dilution. • The granulating solution or binder is prepared. • The powders and the granulating solution are kneaded (pressed) to proper consistency. • The wet mass is forced through a screen or wet granulator.

44. The granules are dried in an oven or a fluidized bed dryer. The dried granules are screened to a suitable size for compression. A lubricant and a disintegrating agent are mixed with the granulation. The granulation is compressed into the finished tablet.

45. Wet Granulation Manufacturing Steps

46. The Dry Granulation Method • The granulation is formed by compacting large masses of the mixture and subsequently crushing and sizing these pieces into smaller granules. • By this method, either the active ingredient or the diluent must have cohesive properties in order for the large masses to be formed • This method is especially applicable to materials that cannot be prepared by the wet granulation method due to their degradation by moisture or to the elevated temperatures required for drying.

47. Direct Compression • In the direct compression of tablets, the tableting excipients used must be materials with properties of fluidity and compressibility. • Some granular chemicals like potassium chloride and methenamine possess free flowing as well as cohesive properties that enable them to be compressed directly in a tablet machine without need of either wet or dry granulation.

48. Tableting excipients having the desired characteristics are used include: Fillers:lactose, microcrystalline cellulose, and dicalcium phosphate; Disintegrating agents:starch, sodium carboxymethyl cellulose Lubricants-magnesium stearate and talc; Glidants:silicon dioxide.

49. Tablet Compression Machines • The basic units in tablet compression machine are two steel punches within a steel die cavity. • The tablet is formed by the pressure exerted on the granulation by the punches within the die cavity, • The tablet takes the size and shape of the punches and dies used.

50. The use of the tablet sometimes determines its shape; • Effervescent tablets are usually large, round and flat, • Vitamin tablets are prepared in capsule-shaped forms. • Tablets prepared using deep-cup punches appear to be round and when coated take the appearance of pills. • Veterinary tablets often have a bolus shape and are much larger than those used in medical practice.