THE UNITED STATES PHARMACOPEIA
`
`THE NATIONAL FORMULARY
`
`By authority of the United States Pharmacopeia/
`Conv_ention, Inc., meeting at Washington, D. C.,
`March 8-10, 1990. Prepared by the Committee of
`Revision and published by the Board of Trustees
`
`Official from January 1, 1995 .
`
`UNITED STATES PHARMACOPEIAL CONVENTION, INC.
`12601 Twinbrook Parkway, Rockville, MD 20852
`
`LUYE1034
`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
`IPR2016-01096
`
`

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`LUYE1034
`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
`IPR2016-01096
`
`

`

`vsP1J
`
`(1151)
`
`1949
`
`General Information 1 Pharmaceutical Dosage Forms
`Transdermal Systems
`SUSPENSIONS
`Transdermal drug delivery s.ystcms. arc sclf~ontaincd~.discretc
`. ns are liquid prep~ra~ions that consist of solid par-
`dosage forms that, when applied to mt.act skm, ar.e d~stgne~ to
`sus~RS'~ed throughout a hqu1~ phase in which the particles
`deliver the drugls) throu~h the skin to the ~ystenuc .ctrculatlon.
`···)eS aas~, ble ()osage forms off&Clally categorized as Suspen·
`so u ·
`·
`h 'f h
`·
`11"
`Systems typically compnse an outer co.venng (barner). a drug
`are oo\ designated .as sue . 1 t. ey are not ancluded in other
`reservoir, which may have a rate controlhng membrane, a ~?ntact
`~ons artcific categones of suspcns1ons, such as Or.al Suspensions,
`adhesive applied to some oral~ par.ts of the system and the S'jstem/
`ll'lor~ srsuspensions, etc. (see th;se other c.ategones). Some sus-
`skin interface and a protecllve hner that ts remov~d before ap-
`toP~~~ arc prepa~ed and ready a or u~e, -.yh1l~ others are prepared
`plying the sy~tem. The activity of these systems ts defined m
`pcns•~T mixtures mtended for conshtut1on JUst before use with
`terms of the release rate of the drug(s) from the system. The
`,s soh priate vehicle. Such products are designated "for Oral
`total duration of drug release from the system and the system
`Jll appr~on .. etc. The term, Milk, is sometimes used for sus-
`susP,t05\0 ~queous vehicles intended for ?ral administration (e.g.,
`surface area may also be stated.
`.
`.
`Transdermal drug delivery systems work by d1ffus1on: the drug
`~~S'0{ Magntsia). ~be te.rm, Magma, 1s often used to describe
`Mtlk 0 ions of inorgamc sohds S';'Cb as clays m water, where there
`diffuses from the drug reservoir, directly o~ th~ougb the rate
`suspcns dency for strong hydrat1on and aggregation of the solid
`controlling membrane and/or contact ad~es1ve ~f presen~. and
`is.~ tenrise to gel-like cons1stency and thixotropic rheological be:
`then through the skin into the $eneral ClrculfitiOn. Typt~ally:
`gtVl~ (e g Bentonite Magma). The term, Lotion, has been used
`modified-release systems are des1gned to prov1de drug deliver~
`bavtoteg~ri~e many topic.al suspensions and emulsions intended
`at a constant rate, such that a true st~ady state bl~ concen-
`tration is achieved and maintained untll the system ts rem~ved.
`10 ~ plication to the .skm (~.g., Calamine Lotion). Some sus-
`fornsi~ns are prepared 1~ stenle ~orm a~d.are U;sed as lnjectables,
`At that time, blood concentration declines at a rate cons1stent
`pe ·ell as for ophthalmic and ot.ac admm1strat10n. These may be
`with the pharmacokinetics of the drug.
`.
`15 ~wo types, ready to use or mt.end~d for constit.ution with a
`Transdermal drug delivery systems arc apphed to body areas
`0~ribed amount of Water for InJect ton or other SUitable diluent
`consistent with the labeling for the product(s) .. As long as drug
`~fore use by the desi@n~ted route. Suspensions should not be
`concentration at the system/skin interface rem~ms constant, the
`amount of drug in the dosage form does not mnuen~c plasma
`· ·ected intravenously or mtrathecally.
`·
`tnJSuspensions inte~de.d fo~ any route of administ~ation shoU;ld
`concentrations. The functional lifetime of the system 1s defined
`contain suitable ant1m1crob1al agents to protect agamst bactena,
`by the initial amount of drug in the reservoir and the release rate
`·east and mold contamination (see Emulsions for some consid-
`from the reservoir.
`NOTE-Drugs for local rather than systemic effect are com-
`~rati~n of antimicr~bial preservative properties that apply also to
`Suspensions). By 1ts very nature, the particular matter m a sus-
`monly applied to the skin embedded in glue on a cloth or plastic
`backing. These products are defined traditionally as plasters or
`nsion may settle or sediment to the bottom of the container
`~pon standing. Such sedimentation may also lead to caking and
`tapes.
`solidification of the sediment. with a resulting difficulty in redis-
`pcrsing the suspension upon agitation. To prevent such problems:
`suitable ingredients that increase viscosity and the gel state of
`the suspension, such as clays, surfactants, polyols, polymers, or
`sugars, should be added. It is important that suspensions always
`be shaken well before use to ensure uniform distribution of the
`solid in the vehicle, thereby ensuring uniform and proper dosage.
`Suspensions require storage in tight containers.
`
`Oral Suspensions
`Oral Suspensions arc liquid preparations containin~ solid par-
`ticles dispersed in a liquid vehicle. with suitable flavormg agents~
`intended for oral administration. · Some suspensions labeled as
`Milks or Magmas fall into this category.
`
`Topical Suspensions
`Topical Suspensions arc liquid preparations containin' so.lid
`particles dispersed in a liquid vehJcle~ intend~d for ar~llcatlo.n
`to the skin. Some suspensions labeled as Lot1ons fat mto th1s
`category.
`·
`·
`'
`
`Otic Suspensions
`O~ic Suspensions are liquid preparation& containing micronized
`Particles intended for· instillation in the outer ear.
`
`Ophthalmic Suspensions
`(See Ophtha!mic Preparations).
`
`SYRUPS
`See Solutions.
`
`SYSTEMS
`In re
`h e been developed
`·
`Using ~~t years, a number of dosage fform~ avniform release or
`targetin ern technology that allows or t e u ts are commonly
`caned d:rof drugs to the body. T~esel proddc f these arc Trans-
`derrnal (!!~cry systems. The most w1de Y use o
`'?Stems.
`
`Ocular System
`Another type of system is the ocular system, which is intended
`for placement in the lower conjuncth·al fornix from which the
`drug diffuses through a membrane at a constant rate over a seven-
`day period (e.g., Pilocarpine Ocular Sysrem).
`
`Intrauterine System
`An intrauterine s)·stem, ba.sed on a similar principle but in-
`tended for release of drug over a much longer period of time,
`i.e., one year, is also available (e.g., Progesterone Intrauterine
`Comraceplive System).
`
`TABLETS
`Tablets arc 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 va.st majority of all tablets manufactured are made by
`compress1on. ~nd ~ompressed tablets are the most widely used
`dosage fo~n~ m. th1s co~ntry. Compressed tablets are prepared
`by the apphcauon of ·htgh p~cssures, utilizing steel punches and
`dt~s, to ~wdcrs '?r granulations. Tablets can be produced in a
`wtde vancty. of s1zes, shapes, and surface markings, depending
`upon the des1gn of the punches and dies. Capsule-shaped tablets
`~re commonly ref~rred to as caplets. Boluses arc large tablets
`mtended for vetennary use, usually for large animals.
`Molded tablets ~re pr~parc~. by forcing dampened powders
`under low .Pressure. mto d1e c~vttles. Solidification depends upon
`crystal bndges butlt up d~rmg the subsequent drying process
`and not upon the compactton force.
`·
`'
`_ Tablet triturates are sm~ll, usually cylindrical, molded or com-
`pres~ed tablets .. Tablet tnturat~s were trad~tionally used as dis-
`p.ensmg tablets m order to prov1de a convement. measured quan-
`tity of a potent drug for compounding purposes. Such tablets
`are rarely used today. Hypodermic tablets are molded tablets
`made from cmt~pletely and readily water-soluble ingredients and
`formcrl¥ ~c~e ~~tended for use in making preparations for hy·
`podernu~ tnJ.e~tt<~n. Th~y arc employed orally, or where rap1d
`drug avadabt!tty ~~ r~quued such as in the case of Nirroglyc~rin
`Tabltts, subhngually.
`Buccal tablets arc intended to be inserted in the buccal pouch
`and sublingual tablets are intended to be inserted beneath tb~
`
`LUYE1034
`Luye Pharma Group Ltd., et al. v. Alkermes Pharma Ireland Ltd.
`IPR2016-01096
`
`