`
`THE NATIONAL FORMULARY
`
`By authority of the United States Phannacopeial
`Convention, Ina, meeting at Washington, DC,
`March 9—12, 1995. Prepared by the Committee of
`Revision and published by the Board of Trustees
`
`Official from January 1, 2000
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`
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`UNITED STATES PHARMACOPEIAL CONVENTION, INC.
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`1260l Twinbrook Parkway, Rockville, MD 20852
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`IPR2018-0039O
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`USP 24
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`General lnfomtatt'on / (1151) Pharmaceutical Dosage Forms
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`2117
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`applied to some or all pans of the system and the system/skin
`interface. and a protective liner that is removed before applying the
`system. The activity of these systems is defined in terms of the
`release rate of the drug(s) from the system. The total duration of
`drug release from the system and the system surface area may also
`be stated.
`
`Transdermal dnrg delivery systems work by diffusion: the drug
`diffuses from the drug reservoir. directly or through the rate con-
`trolling membrane and/or contact adhesive if present, and then
`through the skin into the general circulation. Typically. modified-
`release systems are designed to provide drug delivery at a constant
`rate. such that a true steady state blood concentration is achieved
`and maintained until
`the system is removed. At that time. blood
`concentration declines at a rate consistent with the pharrnacokinetics
`of the dmg.
`Transdennal drug delivery systems are applied to body areas con-
`sistent with the labeling for the product(s). As long as drug con-
`centration at
`the system/ skin interface remains constant.
`the
`amount of drug in the dosage form does not influence plasma con~
`centrations. The functional lifetime of the system is defined by the
`initial amount of drug in the reservoir and the release rate from the
`reservoir.
`
`NOTE—Drugs for local rather than systemic effect are commonly
`applied to the skin embedded in glue on a cloth or plastic backing.
`These products are defined traditionally as plasters or tapes.
`
`Ocular System
`Another type of system is the ocular system. which is intended
`for placement in the lower conjunctiva] fornix from which the drug
`diffuses through a membrane at a constant rate (e.g.. Pilacarpt‘ne
`Ocular System).
`
`Intrauterine System
`An intrauterine system. based on a similar principle but intended
`for release of drug over a much longer period of time. i.e.. one year.
`is also available (e.g., Progesterone Intrauterine Contraceptive
`System).
`
`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 un-
`pleasant after-taste. These tablets have been used in tablet fon‘nu—
`lations for children. especially multivitamin formulations. and for
`the administration of antacids and selected antibiotics. Chewable
`tablets are prepared by compression. usually utilizing mannitol. sor-
`bitol. 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 sub-
`stances and a diluent usually consisting of lactose and powdered
`sucrose in varying proponions. 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 allowad 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 alu-
`minum 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 lac-
`tose. starch. dibasic calcium phosphate. and microcrystalline cel-
`lulose. Chewable tablets often contain sucrose. mannitol. or sorbitol
`as a filler. Where the amount of active ingredient is small. the over-
`all tableting properties are in large measure determined by the filler.
`Because of problems encountered with bioavailability of hydropho-
`bic 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. meth-
`ylcellulose. 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 disintegrat-
`ing agent is starch. Chemically modified starches and cellulose. aL—
`ginic 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 com-
`paction play a role in effectiveness.
`.
`Lubricants reduce friction during the compression and ejection
`cycle. In addition.
`they aid in preventing adherence of tablet ma-
`terial
`to the dies and punches. Metallic stearates. stearic acid. hy-
`drogenated vegetable oils. and talc are used as lubricants. Because
`of the nature of this function. most lubricants are hydrophobic. and
`as such lend to reduce the rates of tablet disintegration and disso—
`lution. 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 con:
`centrations are usually required.
`‘ "
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`TABLETS
`
`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 com-
`pression, and compressed tablets are the most widely used dosage
`form in this country. Compressed tablets are prepared by the ap-
`plication of high pressures. utilizing steel punches and dies. to pow-
`ders 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 lriturates are small. usually cylindrical. molded or com-
`pressed tablets. Tablet triturates were traditionally used as dispens-
`ing 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 com-
`pletely and readily water-soluble ingredients and formerly were in—
`tended for use in making preparations for hypodermic injection.
`They are employed orally. or where rapid drug availability is re-
`quired 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. ch 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.
`
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`rogenic silicas.
`Colorants are often added to tablet formulations for esthetic value
`or or produ t identification. Both D&C and FD&C dyes and lakes
`are used. Most dyes are phomsensitive and they fade when exposed
`0 light. The federal Food and Drug Administration regulates the
`colorants employed in drugs.
`
`make the contained medicament available over an extended period
`of time following ingestion. Expresstons such as “prolonged-ac-
`‘
`' "repeat-action." and “sustained-release" have also been
`
`Uniformity of Dosage Unit: (905)), wherein individual tablets are
`assayed for actual drug content,
`
`is provided (see Disintegration (701)). and
`A disintegration test
`limits on the times in which disintegration is to take place, appro-
`priate tor the types of tablets concerned. are given in the individual
`monographs.
`For drugs of limited water-solubility. dissolution may be a more
`
`(1161) PHARMACY
`COMPOUNDING PRACTICES
`Compounding is an integral part of pharmacy practice and is
`essential to the provrsion of health care. The purpose ol~ this chapter
`and applicable monographs on formulation‘is to provide general
`
`characteristics or criteria that differentiate compounding from man-
`ufacturing include the existence of specific practitioner-patient-
`pharmacist relationships: the quantity of medication prepared in an-
`ticipation of receiving a prescription or a prescription order; and
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`familiar with statutes and regulatinns that govern compounding be-
`cause these requirements vary from state to state.
`The pharmacist
`is responsible for compounding preparations of
`acceptable strength. quality. and ourity with appropriate packaging
`and labeling in accordance with good pharmacy practices. official
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`IPR2018-0039O
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`I-MAK 1010
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`Page 3 of 3
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`I-MAK 1010
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