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Tablets are solid dosage forms containing medicinal substances with or without suitable diluents. They may be classed, according to the method of manufacture, as compressed tablets or molded tablets.
The vast majority of all tablets manufactured are made by compression, and compressed tablets are the most widely used dosage form in this country. Compressed tablets are prepared by the application of high pressures, utilizing steel punches and dies, to powders or granulations. Tablets can be produced in a wide variety of sizes, shapes, and surface markings, depending upon the design of the punches and dies. Capsule-shaped tablets are commonly referred to as caplets. Boluses are large tablets intended for veterinary use, usually for large animals.
Molded tablets are prepared by forcing dampened powders under low pressure into die cavities. Solidification depends upon crystal bridges built up during the subsequent drying process, and not upon the compaction force.
Tablet triturates are small, usually cylindrical, molded or compressed tablets. Tablet triturates were traditionally used as dispensing tablets in order to provide a convenient, measured quantity of a potent drug for compounding purposes. Such tablets are rarely used today. Hypodermic tablets are molded tablets made from completely and readily water-soluble ingredients and formerly were intended for use in making preparations for hypodermic injection. They are employed orally, or where rapid drug availability is required such as in the case of Nitroglycerin Tablets, sublingually.
Buccal tablets are intended to be inserted in the buccal pouch, and sublingual tablets are intended to be inserted beneath the tongue, where the active ingredient is absorbed directly through the oral mucosa. Few drugs are readily absorbed in this way, but for those that are (such as nitroglycerin and certain steroid hormones), a number of advantages may result.
Soluble, effervescent tablets are prepared by compression and contain, in addition to active ingredients, mixtures of acids (citric acid, tartaric acid) and sodium bicarbonate, which release carbon dioxide when dissolved in water. They are intended to be dissolved or dispersed in water before administration. Effervescent tablets should be stored in tightly closed containers or moisture-proof packs and labeled to indicate that they are not to be swallowed directly.
Chewable Tablets
Chewable tablets are formulated and manufactured so that they may be chewed, producing a pleasant tasting residue in the oral cavity that is easily swallowed and does not leave a bitter or unpleasant aftertaste. These tablets have been used in tablet formulations for children, especially multivitamin formulations, and for the administration of antacids and selected antibiotics. Chewable tablets are prepared by compression, usually utilizing mannitol, sorbitol, or sucrose as binders and fillers, and containing colors and flavors to enhance their appearance and taste.
Preparation of Molded Tablets
Molded tablets are prepared from mixtures of medicinal substances and a diluent usually consisting of lactose and powdered sucrose in varying proportions. The powders are dampened with solutions containing high percentages of alcohol. The concentration of alcohol depends upon the solubility of the active ingredients and fillers in the solvent system and the desired degree of hardness of the finished tablets. The dampened powders are pressed into molds, removed, and allowed to dry. Molded tablets are quite friable and care must be taken in packaging and dispensing.
Formulation of Compressed Tablets
Most compressed tablets consist of the active ingredient and a diluent (filler), binder, disintegrating agent, and lubricant. Approved FD&C and D&C dyes or lakes (dyes adsorbed onto insoluble aluminum hydroxide), flavors, and sweetening agents may also be present. Diluents are added where the quantity of active ingredient is small or difficult to compress. Common tablet fillers include lactose, starch, dibasic calcium phosphate, and microcrystalline cellulose. Chewable tablets often contain sucrose, mannitol, or sorbitol as a filler. Where the amount of active ingredient is small, the overall tableting properties are in large measure determined by the filler. Because of problems encountered with bioavailability of hydrophobic drugs of low water-solubility, water-soluble diluents are used as fillers for these tablets.
Binders give adhesiveness to the powder during the preliminary granulation and to the compressed tablet. They add to the cohesive strength already available in the diluent. While binders may be added dry, they are more effective when added out of solution. Common binders include acacia, gelatin, sucrose, povidone, methylcellulose, carboxymethylcellulose, and hydrolyzed starch pastes. The most effective dry binder is microcrystalline cellulose, which is commonly used for this purpose in tablets prepared by direct compression.
A disintegrating agent serves to assist in the fragmentation of the tablet after administration. The most widely used tablet disintegrating agent is starch. Chemically modified starches and cellulose, alginic acid, microcrystalline cellulose, and cross-linked povidone, are also used for this purpose. Effervescent mixtures are used in soluble tablet systems as disintegrating agents. The concentration of the disintegrating agent, method of addition, and degree of compaction play a role in effectiveness.
Lubricants reduce friction during the compression and ejection cycle. In addition, they aid in preventing adherence of tablet material to the dies and punches. Metallic stearates, stearic acid, hydrogenated vegetable oils, and talc are used as lubricants. Because of the nature of this function, most lubricants are hydrophobic, and as such tend to reduce the rates of tablet disintegration and dissolution. Consequently, excessive concentrations of lubricant should be avoided. Polyethylene glycols and some lauryl sulfate salts have been used as soluble lubricants, but such agents generally do not possess optimal lubricating properties, and comparatively high concentrations are usually required.
Glidants are agents that improve powder fluidity, and they are commonly employed in direct compression where no granulation step is involved. The most effective glidants are the colloidal pyrogenic silicas.
Colorants are often added to tablet formulations for esthetic value or for product identification. Both D&C and FD&C dyes and lakes are used. Most dyes are photosensitive and they fade when exposed to light. The federal Food and Drug Administration regulates the colorants employed in drugs.
Manufacturing Methods
Tablets are prepared by three general methods: wet granulation, dry granulation (roll compaction or slugging), and direct compression. The purpose of both wet and dry granulation is to improve flow of the mixture and/or to enhance its compressibility.
Dry granulation (slugging) involves the compaction of powders at high pressures into large, often poorly formed tablet compacts. These compacts are then milled and screened to form a granulation of the desired particle size. The advantage of dry granulation is the elimination of both heat and moisture in the processing. Dry granulations can be produced also by extruding powders between hydraulically operated rollers to produce thin cakes which are subsequently screened or milled to give the desired granule size.
Excipients are available that allow production of tablets at high speeds without prior granulation steps. These directly compressible excipients consist of special physical forms of substances such as lactose, sucrose, dextrose, or cellulose, which possess the desirable properties of fluidity and compressibility. The most widely used direct-compaction fillers are microcrystalline cellulose, anhydrous lactose, spray-dried lactose, compressible sucrose, and some forms of modified starches. Direct compression avoids many of the problems associated with wet and dry granulations. However, the inherent physical properties of the individual filler materials are highly critical, and minor variations can alter flow and compression characteristics so as to make them unsuitable for direct compression.
Physical evidence of poor tablet quality is discussed under Stability Considerations in Dispensing Practice 1191.
Tablets are required to meet a weight variation test (see Uniformity of Dosage Units 905) where the active ingredient comprises a major portion of the tablet and where control of weight may be presumed to be an adequate control of drug content uniformity. Weight variation is not an adequate indication of content uniformity where the drug substance comprises a relatively minor portion of the tablet, or where the tablet is sugar-coated. Thus, the Pharmacopeia generally requires that coated tablets and tablets containing 50 mg or less of active ingredient, comprising less than 50% by weight of the dosage-form unit, pass a content uniformity test (see Uniformity of Dosage Units 905), wherein individual tablets are assayed for actual drug content.
Disintegration is an essential attribute of tablets intended for administration by mouth, except for those intended to be chewed before being swallowed and for some types of extended-release tablets. A disintegration test is provided (see Disintegration 701), and limits on the times in which disintegration is to take place, appropriate for the types of tablets concerned, are given in the individual monographs.
For drugs of limited water-solubility, dissolution may be a more meaningful quality attribute than disintegration. A dissolution test (see Dissolution 711) is required in a number of monographs on tablets. In many cases, it is possible to correlate dissolution rates with biological availability of the active ingredient. However, such tests are useful mainly as a means of screening preliminary formulations and as a routine quality-control procedure.
Tablets may be coated for a variety of reasons, including protection of the ingredients from air, moisture, or light, masking of unpleasant tastes and odors, improvement of appearance, and control of the site of drug release in the gastrointestinal tract.
Classically, tablets have been coated with sugar applied from aqueous suspensions containing insoluble powders such as starch, calcium carbonate, talc, or titanium dioxide, suspended by means of acacia or gelatin. For purposes of identification and esthetic value, the outside coatings may be colored. The finished coated tablets are polished by application of dilute solutions of wax in solvents such as chloroform or powdered mix. Water-protective coatings consisting of substances such as shellac or cellulose acetate phthalate are often applied out of nonaqueous solvents prior to application of sugar coats. Excessive quantities should be avoided. Drawbacks of sugar coating include the lengthy time necessary for application, the need for waterproofing, which also adversely affects dissolution, and the increased bulk of the finished tablet. These factors have resulted in increased acceptance of film coatings. Film coatings consist of water-soluble or dispersible materials such as hydroxypropyl methylcellulose, methylcellulose, hydroxypropylcellulose, carboxymethylcellulose sodium, and mixtures of cellulose acetate phthalate and polyethylene glycols applied out of nonaqueous or aqueous solvents. Evaporation of the solvents leaves a thin film that adheres directly to the tablet and allows it to retain the original shape, including grooves or identification codes.
Where the drug may be destroyed or inactivated by the gastric juice or where it may irritate the gastric mucosa, the use of “enteric” coatings is indicated. Such coatings are intended to delay the release of the medication until the tablet has passed through the stomach. The term “delayed-release” is used for Pharmacopeial purposes, and the individual monographs include tests and specifications for Drug release (see Drug Release 724) or Disintegration (see Disintegration 701).
Extended-release tablets are formulated in such manner as to make the contained medicament available over an extended period of time following ingestion. Expressions such as “prolonged-action,” “repeat-action,” and “sustained-release” have also been used to describe such dosage forms. However, the term “extended-release” is used for Pharmacopeial purposes, and requirements for Drug release typically are specified in the individual monographs.