Introduction
`to
`Pharmaceutical Dosage
`Forms
`
`Howard C. Ansel, Ph.D.
`
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`LEA & FEBIGER [~]I'HILA11ELPHIA
`
`1981
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 1
`
`

`

`Dosage Forms and Routes
`of Administration
`
`lhtJ<; substances are seldom administered in
`their natural or pure state. but rather as part of
`a formulation in combination with one or more
`nonmedicinal agents that serve varied and spe(cid:173)
`cialized pharmaceutical functions. Through se(cid:173)
`lective use of these nonmedicinal agents. re(cid:173)
`ferred to as phannaceulic inyredie11ts. aids.
`adjuncts. or necessities, pharmaccu tical prepa(cid:173)
`rations of various types result. The phannaceu(cid:173)
`tic ingredients -;olubilize. suspend. thicken. di(cid:173)
`lute. cmulsifv, stabilize, preserve. color. flavor,
`and fashion the many and varied medicinal
`agents into efficacious and appealing pharma(cid:173)
`ccu tical preparations. Each di ffcrcn t type of
`preparation is unique in its physical and phar(cid:173)
`maceutical characteristics and in the final form
`in which the drug is presented to the patient.
`These varied preparations. which provide the
`manufacturing pharmacist with the challenges
`of formulation and the physicLm with the
`choice of pharmaceutical tvpes. arc termed
`··dosage forms.·· The general area of studv
`which concerns itself with the physicaL chemi(cid:173)
`caL and biological factors which intluence the
`formulation. manufacture. stabilitv. and effec(cid:173)
`tiveness of pharmaceutical dosage forms
`is
`termed plza mzau•u tics.
`
`The Need for Dosage Forms
`The potent nature and low dosage of most of
`the drugs in use today precludes anv expecta(cid:173)
`tion that the general public could safclv obtain
`
`the appropriate dose of a drug from the hulk
`material. The vast majority of drug substances
`arc administered in milligram amounts, IIIlich
`too small to be weighed on anything but ;1 sensi(cid:173)
`tive laboratorv balance. For instance, how could
`the lavman accurately obtain the 325 mg of as(cid:173)
`pirin found in the common aspirin tablet from a
`bulk supply of aspirin'! lie couldn't. Yet. com(cid:173)
`parcel with many other drugs, the dose of aspi(cid:173)
`rin is formidable (fable :3- I). For example, the
`dose of cthinyl estradiol, 0.0.'5 mg. is l, 6500 the
`amount of aspirin in an aspirin tablet. To put it
`another wav. 6.'500 cthinyl estradiol
`tablets.
`each containing 0.05 mg uf drug, could be made
`from an amount of ethinyl estradiol equal to the
`amount of aspirin in just one aspirin tablet.
`When the dose of the drug is minute. as that for
`ethinyl estradioL solid dosage forms such as tab(cid:173)
`lets and capstlles must he prepared with fillers
`or diluents su that the size of the resultant dos(cid:173)
`age unit is large enough to pick up with the lin(cid:173)
`e;ertips.
`l n a deli lion to providing the mechanism for
`the safe and convenient clcliverv of accurate
`dosage, dosage forms are needed for the follow(cid:173)
`ing and other reasons:
`
`I. For the protection of a drug substance from
`the destructive inHuences of atmospheric
`oxvgen or moisture (e.g. coated
`tablets,
`scaled ampules).
`2. For the protection of a drug substance from
`the dcstmctivc influence of gastric acid
`
`
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 2
`
`

`

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`(t'.g. enteric
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`after oral administration
`coated tahkts 1.
`:t To l'Ont'(•al the hitter. saltY. or obnoxious
`taste or odor of a drug suhstallC(' (<'.g. cap(cid:173)
`sules. coatl'd tablets. flavored syrups 1.
`-1. To prm·ide
`liquid pn•parations of sub(cid:173)
`stances that an· either insoluble or unstable
`in the d(·sin·d \'ehicll• (<'.g. suspensions!.
`fl. To pro\·idl' liquid dosage fornts of Stlh(cid:173)
`stancl'S soltthlc in tlw dl'sired vl'hicl(' (e.g.
`solutions 1.
`'li> prm·id•· cxtcnclcd drug action through
`controlil'cl release nH.'chanisuJs I e.g. ,·arioth
`controlled release tablets. capsttks and sns(cid:173)
`pcnsions 1.
`7. T'o pro\'id<' optin1al dru~ action fron1 topi-
`cal administration sitl•s 1 e.g. ointments.
`creams. oplt thai mil'. car. and nasal prepa(cid:173)
`rations).
`H. To pro,·idc for the insertion of a drug into
`
`li.
`
`otH' of the l>o(l\··s orific<'s (!'.g. n·t·tal or vagi
`na I suppositories 1.
`q To pro,·idc for
`the plact'lll!'nt of dmgs
`within ho(h tissiJ('S (e.g. iliJ!'l'lionsl.
`10 To provide for optimal drug action through
`iltltalation thn:ql\ (e.g. inhalants and inh:t(cid:173)
`lat ion aerosols I.
`
`In addition to the abo\'('. 111an\' dosage forms
`p<'rmit cas!' of drug idC'ntification through dis-
`1 inc! in'lll'SS of color_ shape. or
`identilving
`111arkings.
`
`The Variety of Dosage Forms
`ThC're arc manv different for111s into which a
`medicinal agent lila\' be placed lor the conven(cid:173)
`i!'nt and dlicacious treatment of disease. Drugs
`can h(' pr<'parccl for administration hv C\'el'\
`concc•ivahk routt•. and the appropriate pharma(cid:173)
`c<'tltical preparation formulated to insure maxi(cid:173)
`mum therapeutic response. Tables :1-2 and :)-:)
`prl'st·nt tlw various rotltl's of dnt.l!. administra(cid:173)
`tion and the most coJnntonlv utilized dosagl'
`forms.
`Some individual medicinal agents arc cfft'l'(cid:173)
`li\'e therapl·utic agents for maladies of various
`parts of the hodv :md an• formulated into a half
`dozen or more dosage
`forms of varvi ng
`strengths. l'ach having the particular pharma(cid:173)
`ceutical charal'leristics which lend themselves
`best to a specific application. One such vcrsatil<(cid:173)
`drug is prednisolone. a svntlwtic adrenocortical
`steroid. us(•d primarilv for its anti-inflamma(cid:173)
`ton act ivitv. In the USP XX. prednisolom· and
`its various chemical forms arc officially rccog(cid:173)
`nil<'d as:
`
`ta 1 Prednisolone. the chemical powder used in
`phanuaceu tic a I com pounding. particular h
`in the prep:tration of (bland tc).
`1 hi Prcdnisolom· Tabkts. liSl'd oralh for the
`svsll'lllic action of prednisolone.
`(cl Prednisolone Cream. for topical application
`to the skill.
`1 cl l l'reclnisoloJH' Tcbutatc. :1 slight tv soluble in
`watn compotmd. used in the form of aster(cid:173)
`ile suspension as an intra-articular. intra(cid:173)
`bursal. allCI soft-tissue injection.
`((') Prednisolonl' Acetate. the acetate ester form
`of prednisolone. used primarilY in the prep(cid:173)
`aration uf (fl.
`( f1 Sterile Pr<'dnisololll' Acetate Suspension.
`
`
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 3
`
`

`

`48
`
`Introduction to Pharmacezttical Dosage Forms
`
`Table 3-2. RourF.s OF DReG
`ADMINISTRATION
`
`Term
`
`Site
`
`oral
`peroral (per os 1 )
`
`sublingual
`parenteral
`
`intravenous
`intraarterial
`intracardiac
`intraspinal or
`intrathecal
`intraosseotis
`in traart i cula r
`intrasynovial
`intracutaneous or
`intradermal
`subcutanL•ous
`in tram usc ular
`cpicutaneous (topical l
`conj unetival
`intraocular
`intranasal
`:tural
`intrarespiratorv
`rectal
`vaginal
`methral
`
`IIIOUth
`gastrointestinal tract
`via mouth
`under the tongue
`other than the gastro(cid:173)
`intestinal tr:1ct
`1 by injection l
`vein
`artery
`heart
`spine
`
`hone
`joint
`joint-fluid area
`skin
`
`beneath the skin
`muscle
`skm surface
`conj UIH.:tiva
`eve
`nose
`car
`lung
`rectum
`vagina
`urethra
`
`'The abbreviation "p.o." is commonly t;mplovcd on pre(cid:173)
`scriptions to indicate to be sw:tllowl•d.
`
`employed as an intra-articular and intra(cid:173)
`muscular injection.
`(g) Prednisolone Sodium Phosphate, a water
`soluble salt form of prednisolone, used pri(cid:173)
`marily in the preparation of (h) and ( i).
`(h) Prednisolone Sodium Phosphate Injection,
`an aqueous solution used for intravenous or
`intramuscular injection.
`(i) Prednisolone Sodium Phosphate Ophthal(cid:173)
`mic Solution, an aqueous solution for topi(cid:173)
`cal application to the eye.
`(j) Prednisolone Succinate, a slightly soluble
`in water compound, used in the preparation
`of (k).
`(k) Prednisolone Sodium Succinate for Injec(cid:173)
`tion, a sterile powder, prepared from so(cid:173)
`dium succinate with the aid of sodium car(cid:173)
`bonate. At the time of use it is prepared into
`a solution and used by intramuscular or in(cid:173)
`travenous injection.
`
`Table 3-3. DosAGE FoH:vl APPl.lCAT!ON
`
`Houte of'
`:\ d 111 i 11 is t ra tir m
`
`oral
`
`sublinl!;tl:ll
`
`parenteral
`
`epicutaneous
`
`conjunctival
`
`intraocular/
`intraaural
`
`intranasal
`
`in trarcspiratory
`
`rectal
`
`vaginal
`
`methral
`
`l'rinwry Dosage Forms
`
`tablets
`capstlles
`solutions
`svrups
`elixirs
`suspensions
`magmas
`gels
`powders
`
`tablets
`troches or lozenges
`
`solutions
`suspensions
`
`ointments
`crt>ams
`pastes
`plasters
`powders
`aerosols
`lotions
`solutions
`
`ointments
`
`solutions
`suspensions
`
`solutions
`sprays
`inhalants
`ointments
`
`aerosols
`
`solutions
`ointments
`suppositories
`
`solutions
`ointments
`emulsion foams
`tablets
`suppositories
`
`solutions
`suppositories
`
`13y creating special chemical forms of the
`basic chemical prednisolone, research pharm(cid:173)
`acists have facilitated the preparation of ef(cid:173)
`fective anti-infl:.lmmatory pharmaceuticals of
`prednisolone for use orally, by injection as a
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 4
`
`

`

`sllsp<'llsion or sollltion. :u1d I'm topical applic:l(cid:173)
`tion to til<' skin and e\1'.
`1!1 :uldit loll I<J prcdJiisoloJH' otiH'r drugs arl'
`pn·parl'd
`Ill
`IIIIIIH'I'OIIS
`closag<•
`f'oi'IIIS
`:IIIli
`str<'ll).!.t!Js f'lll'
`tiJl' l'fliL·:I<'i<lllS
`:IIHI
`l'OII\'I'lli<•JJI
`trealllll'lll of disl'as<· (S<'<' l<'igiJn· :~-I). Bd'orl' a
`llll'dil'illal age111 is lol'lllllLit<·d i111o oil<' or lli<JI'<·
`dosag<' l'oi'IJIS. aliiiJJig tlu· f'al'lors which IIIIlS! lw
`L'llllsid<'J'l'd an· Slll'h tlll'rap<'llli<· Jllattns as
`til<'
`Jlallll'<' of till· illlll's". till' Jllallll<'l' i11 whil'll it is
`g<·m·ralh
`tr<·at<·d. lol'allv or through svsl<'lllil'
`;ll'tioll. and tlw ag<· and :111ticipated l'ollditioJJ of
`til<· p:lti<'lll
`
`lating to lir11g allsorptio11. SoiiJl' 111a\ Ill· w<·ll :dJ(cid:173)
`sorl)('d fro111 a giw•JJ roulc of admillistr;JtioJJ.
`w h<•J'<•as ot h<'rs ma v IJ<' poorh· a l>sorl>cd. l·:al·IJ
`dnll!, JliiJst
`Ill' indi\'id11alh l'\ alll:ltl'd and til<'
`IIIOst ellkacioiJS routcs det<•ntlin<·d and dos;l,).!.l'
`for111s prcparcli.
`I >rug ... illtl'JJd<·d to provid<· localit.<·d ell l'l'ts
`an· appli<'d di1w:th to till' sit<· of tll<·ir illl<'JHicd
`:Jcti<JII. This includes IIJ<JSI of the prodJJcts uti(cid:173)
`lit<•d
`i11
`tiH· <'Vl'. l'ar. IIOS<'. throat. as w<•ll as
`t hosl' appli<•d to tit<· skill or placl'd ill tIll' vagina
`or rcctlllll or S\\allm\cli f<Jr
`I<Jl·alit<·d dkt·ts
`withi11 till' gastroint<·stiJial tract.
`
`Therapeutic Considerations
`in Dosage Forn1 Design
`Till' JlallJI'<' <JI' till' diseasl' or illn<·ss against
`\\ hicl1 till' drng Js intended is an ess<·ntial coJJ(cid:173)
`sid<·rati<Jil i11 d<Tiding which dusag<' l'onu.s of a
`drug to prepare and Jllarkl't Such hasic lfli<'S
`t lolls as whl't l!l'r tlw disl'asl' is best treat I'd svs(cid:173)
`l<'lllil':dh Ill' local!\ IIIllS[ hi' aiiSWered. and tiJl'
`Jn<Jst appropri:lt<' dosag<· for111s pn·p:ln·d and
`l'Valuatcd ill clillicaltrials. Ass<•ssllll'llls must lw
`madl' as to wh<•thl'r th<· illlll'Ss is best tn•ated
`with prolllpt-. slow-. short-. or long-acting phar(cid:173)
`Jnan'lllicals. If then· is thl' renwtest chaJICl' tlwt
`a giVl'll drug IIJ:I\' hav<· applicatio11 to an <'llll'l·
`gcncv situation or o1w ill which the patil'llt is
`t'oJJJ:Itosl'. or unlikl'l\' to tak<· oral nll'dil'ation. a
`t'or111 suitable for parenteral administr:ltioJJ ma\
`Ill' developed. If thl' illm·ss is Olll' that can geJI·
`l'l'alh be trl'at<·d sall'lv thro11gh tlw selt'-adJIJill(cid:173)
`istration of thl' drng. maJJUfactllrl'r·s oblige IJ\
`placing tlw dr11g in l'lllllpact ctosag<' Ullits SIJch
`as tablets or c:lpslJles or ill l'asilv adJninistnl'd
`liquid forms. In th<· vast 111ajoritv of instanu•s.
`dr11g mallllfactlll'<'rs prep;ll'l' a singl<· llll'dil'illal
`agl'llt into Sl'\'cral dosag<· forms. parth to satisfv
`till' perso11al prd<·rcJH'l' of th<' phvsil·JaJI or pa·
`tJcJll ;u1d part!\ to nl<'l't th<· p<'l'llliar ll<'<·ds or
`r<'<jllil'l'llll'nts of a cl'r(;JJII sillJation. !·or 111
`staJJl'l'. drugs usl'd to l'Olllhat nausea and vomit(cid:173)
`ing 111;1\ hi'
`tak<·n propll\'l:icticalh
`ill
`t:dllt·t
`form. as before boarding an airplane or for th<'
`lll<JI'IIillg sid.JH•ss of prq~11a11n. hut this fonn
`111a\ he of littk valul' if gin•11 during the co11rs<·
`of thl' illlll'SS lJl'C:IIISe it lila\' Ill' Sjll'\\'l'cl With the
`vomit11s. Vor this rl'aSOJI s11ppositories are also
`made a\'aii:Jble for US<' when n•qJJired. Thev are
`particularh useful in treating infants. l~<~ch
`drug has its own indi\·idual clwr;Jl'leristics r<··
`
`The Aye of' /h(' Patient
`Tlw :1g1· of till' int<·nd<·d patie11t has a pro(cid:173)
`IIOllnl'l'd inii!Jelll'l' on the tYp<·s of dosage !'onus
`prqJ:UHI for a gi\l•n dn1g
`l·or inl'a11ts :uHichil(cid:173)
`dn•JJ 11ndn :> vcars of ag<'. pharnJ:Il'l'lltical liq(cid:173)
`llid.s rat Iter tha11 solid dosagl' forms an· prc(cid:173)
`fennl for oral ad111inistration. These liq11ids
`which arl' generallv flavored aqueous solutions.
`S\TIIps or SIISj>eiiSions. arc liSUall\' administl'J'l'd
`dir<·cth into the infant·~ or child's mollth or
`illcmporat<•d with his food ( Fi.l!. J-2). t\ SJIIgk
`liquid pediatric preparation mav b<· llsed for in(cid:173)
`fants a11d children of all ages. with thl' dos<· of
`till' drug \·ari<·d IJ\
`tiH· vuluJm• administered.
`\\'hen an infant is in the throes of a vomiting
`crisb. is gagging. hns a productive cough. or is
`si111plv rell<·llious. there nwv lw sollJe qiJestion
`as how IIIlich of thl' medicine administered is
`actualh swallovved and how much is cxpl·cto(cid:173)
`rated. In such insta11ces. injections maY be rc(cid:173)
`lJIIin•d. Infant sizt• rectal suppositories mav also
`be em plowcl although drug absorption from the
`recllJnJ is erratil' and unckpendabk.
`The mal nJJJte is preferred when administer(cid:173)
`ing nwclication
`to children. However. with
`m:1nv children then· is a problem of' c<JIIlpliaJHT
`with till' prescribed dosage reginl<'IJ.
`l11 thcsl'
`insta11n•s. dosag<· forms which allow rl'(luu·d
`l'requcnc\ of administration m;1\' be cnlplov<·d
`tu advantage on'!' thos<· req11iring gr<'ater fr<·(cid:173)
`qllellc\' of administration. This mav !Jc partictl(cid:173)
`larh true for children who ma\ be scheduled to
`tak<· Illedication whil<· at .~chool. In instances i11
`which complianc<· is an ;Jbsolute necessitY and
`cannot be guaranteed through self-administered
`oral nwdicatio11. parl·nt<•ral lh(T:IjJ\' mav bl' n·(cid:173)
`quired.
`During earh childhood and soml'liJm•s in
`latn \<'ars. a
`\Ollllgster Ilia\ han· difliudt \
`
`
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 5
`
`

`

`SO
`
`l11tmduction /o Phanl/accutical f)osaye For111s
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`,..,·f;
`
`Fig. 3-l. 1~.\1/Hlfiil·.~ o( the· nnic·d dmaqc (onus of' 11 dmy 1//ar/u·tcd hy 11 pllaniiiHTIIfica/uwuu(al'/un·r to llll't'/ the
`spc·r·ial n·quircmc'llfsof 1/w f!Citit•nf. Cloclni'isc·. (mlllllf!fJC'r /1'('1. om/ clrnfJ.~ (susfH'IIsiull firt'fllll't'ci hlJfiiWmllld.~l on
`I'I'CIJII.~/i/ufioll of' ,4rllllllfc·.~) (or f!l'dillfric fJCific'll/; ,41'111111/t'.~ ltlr I'I'C0/1.~/i/11/ioll /o f)l'('f)(/rl' om/ ~~~~/il'll.~iOII !lc/lllilli.~·
`/I' rl'll hy .~poo 11: IiI 111-coa I t•t! fa /J/1'1.~ u( two s I rl'nq I II.~: sululit !II.~ I I' r 111 Ira 11111 .~I ·uta r i II}I'C lio 11: ui 11 I lilt' 11 I II u· I tJfJica I 11 ·'c':
`colnhiualion tu/J/1'1 ll'ith anotlwr IIIC'clidnal UtJt'llf: s/t'nlt· lyupluli::l'tlf!UU'dn (or tilt' f!l't'fHIIHflu/1 o/'aJJ inlml'CIIull.,
`,,ofution: aud 11 prl'pllrcd fJt'tliatric um/ .wspl'n.~io/1. I ('ourlt'.~l/ u( ,.\hho/1 La/}t)m/orit'SI
`
`swallowing solid dosage forms. especiallv whole
`tablets. For this reason. many medications in(cid:173)
`tended for youngsters are formulated as chew(cid:173)
`able tabl<'ts which mav he• broke11-11p in the
`mouth before swallmving. \Jan\' of these tabkts
`arc comparable in texture to an after-dinner
`mint and break down into a pleasant t:tsting
`crcamv material. Capsules have been found bv
`manv to be 1110re easilv sw:1llowed than whole·
`tablets. If a capsule is allowed to hec<Jllle 111oist
`in the mouth before swallowing, it becomes
`slippcn· and slides down the thro:tt more readih·
`with a glass of water. In instances in which a
`child has clillicultv swallmving a capsule. the
`
`contents mav he en1pt ied into a spoon. 111ixl'd
`with jam. lwnev. or otller silllilar rood. to mask
`the taste of the medicatiou, and swallmved.
`,\dulls arc generallY intercst<'d in coll\'l'll·
`i<'llce. and when drul!,s arc to ht' carri<'d about
`:111d taken awav from lrollll'. solirl dos:1ge l'onns
`are preferred. With solid dosage fonns there is
`no inconvenience of measuring spoons. stickv
`bottles. or large t·ontainers as there is witl1 liq·
`11id pharn1aceutic:ds. One tahl<'l or caps1de 111av
`he easilv carried. hut one teaspoon of n1edica·
`tion may not. Unqucstionahlv. solid dosage
`forms arc the most conv<'nient :111cl poptdar
`forms of pharmaceuticals.
`
`
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 6
`
`

`

`/)usU</1' /-ul'l/1.~ 11111! llulltr·~ uf i\dlllilli~lmliull :>I
`
`;\II solid dos:l).!,<' loriiiS. tahlt·ts. and t·apsult·~
`IIlllS! IH" ol a silt' :111<l sllapt• c:1sih S\\ allowed.
`l·or drill!," l'fi<Ttin· onl\ in cxtr:1 Ia!').!,<' doses.
`IIIOrt' than a singll' tahlt•t o1· capsul<· lila\ consti(cid:173)
`tlltt· tilt' usu;d dosl' to I)(' tak<·n.
`.\1:111\ <·l<lcrh pat l<'llls tak<· IIIII It ipl<· nwdil·:1
`1 ion., d: li I\'. Th< · IIIOIT dis t i Ill'! I\' t' tIll' s i /.t'. sha Jll'.
`:111d color ol solid dosagt• lorlllS. til<' casit•r is tl1<·
`pmpcr idcntilicatioll ol till' nwdil'ations. 1:<·(cid:173)
`caust· ol tiH•Jr lllldt ipll' drug tiH"r:ql\ aiHI rt··
`clllt'l'd ('\'l'Sight. tlH'rt• :ll'l' lrl'l{lll'lll t'ITOrs ill l:lk
`ing
`lllt'dicat ions anlollg
`t ht· clderh. Dosagl'
`lorms which allow n·dlllTcll'n·qu<·ncv ol adlllill(cid:173)
`istr;llion witlw11t sanifict• ol' l·flil·it•lll'\ are ad(cid:173)
`v a 11 tagCOIIS.
`\lan\ older pt'I'SOIIS have diflicult\ ill swal(cid:173)
`lm\·illg and tlliiS large tablets a1HI L·:q>slill's an·
`l'rcqtiL'lllh a\oidcd
`!\1<-dications illl<'IH!t-d
`l'or
`
`till' clderh :ll'l' l'OIIIIIIOIIh l'orllllllatcd into or:d
`I iqtl ids.
`requires
`l'rt•qll<'llth
`t•ldcrl\ patient
`Th<·
`s111alkr doses ol so111e drugs tha11 arc custolll:lr(cid:173)
`ih gi\'t'll to \<lllllg :lthdts. 'I'll is is l:irgel\ due to
`redt1ced drtl.l!. llll'taholisnl a11d l'l illlillation ftlllL'·
`t i<>lls ill tiH· t'ld<·rl\ pat it•nt. :\s a l't•sult. drug
`products lor the elderlY IIIIlS! providl' varving
`dnrg stl'l'lll!,ths or llt'xihil' dosagt· administratioll
`1 :ts with liqt1ids 1 to pcn11it dosi11g ad,illslllll'llls.
`
`Routes of Drug
`Ad1ninistration
`The following d iscussio11
`\Vi II brieflY trca t
`till· tiStlal rout<'s ol drug achnillistratioll and the
`dosage form~ lnost 11 t i I i;.t•d through t"ach.
`
`I
`
`/
`
`I
`
`Fig. 3-2. "/'r·r· /kl' no~(·" hmud u('umlliljllid disp('/1.~('1' 1/.,l'rJ tu admittisfl'l' 1//('(/S//I'Pd ro/l/1/1('.\ u(' filtllid 11/l'rlicatiutt
`fu yutlll.l/.~fiT.~ 1 Cu/11'11'.'11 uf Ba.\!l Cutpomtiuttl
`
`
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 7
`
`

`

`.12
`
`Introduction to Pltannac<'lltical /)o.wuw Form ....
`
`The absorption of drug substattet•s is a most
`important factor in the sell'ction of the appro(cid:173)
`priate route of administration. in the destgn of
`the most eHicaciotts dosage t'ornts. and there(cid:173)
`fore. in dntg therapv. Although Ltctors illllll(cid:173)
`l'ncing the absorptiun of dntgs :tn• covered in
`detail in the tH'Xt chapter. sotne of these factors
`specific to certain dosage forms or rotttes uf
`administration :m• bril'flv itllroduced here.
`
`Oral Houte
`
`Drugs :~re most frequentlv taken hv oral :1d(cid:173)
`ministration. Although a few drugs taken orallv
`arc intended to he dissolved within the tnouth,
`the vast tnajorit v of drugs taken ora ltv are swal(cid:173)
`lowed. Of these. the 111:1joritv :1re taken for the
`. .,lfs/elnic drug dt'ects that result after absorption
`from till' v:trious surfaces along the gastrointes-
`1 inal tract. A few dnw;s arc swallowed for their
`local :tction within the confines of the gastroin(cid:173)
`testinal tract. made possible by their insolubil(cid:173)
`itY and 'or poor absorbabilitY from this route.
`Compared with alternate routes. the oral
`route is considered the most natural. uncumpli(cid:173)
`(·ated. convenient. and safe means of adminis(cid:173)
`tering drugs. Disadvantages of the oral route
`include slow drug response r when compared
`with parentcrallv administered drugs); chance
`of irregular absorption of drugs. depending
`11pon such factors as constitutional make-up.
`the amount or t\·pe of food present within the
`_gastrointestinal tract; and the destntctiutt of
`certain drugs hv the acid reaction of the stom(cid:173)
`:1ch or bv gastrointestinal enzymes. Perhaps tht•
`111ost notable ('Xamplcs of the latter are the \·ari(cid:173)
`ous preparations of insulin. all of which tnttst
`lw administer<>d parenterallv due to the dcstntc(cid:173)
`t ion of this hormonal protein substance bv the
`prott•olvtic enzvntL'S of
`the gastrointestin:d
`tract. The 1111CL'rtaintv nl' maintenattce of the
`prescribed dosage re~imen when tht· tm•dication
`is in the hands of the patient is a distinct possi(cid:173)
`hilitv, and 1111douhtcdlv manv instanu's of over(cid:173)
`dosage or undcrdosagc with sclf-administ£·rcd
`drugs n'sttlt. ,\ltlwul!,h error in dosagL' is a dis(cid:173)
`advantal!,t' inhNL'nt in all tvpcs of sl'lf-adminis(cid:173)
`ll'n·d drugs. not onlv the more comnton oral
`t\ pes. there is no compll'lelv t'fl'cl'live :dterna(cid:173)
`tive. :\clt•quate guidance in the pmper 11se of
`drugs m11st he pmvidcd him hv tltc• plnsiL·iatt
`and the pharmacist.
`DOSAGE FORMS APPLICABLE. Dntgs :liT :td-
`
`ministen'd hv the or:d route in a vari<'l\' ol' phar(cid:173)
`nwceutical forms. <'ach with inhcn'nt therapeu(cid:173)
`tic advantages that result in their selectiH' use
`hv phvsicians. The most popttlar forms arc tah(cid:173)
`IPts. capsules. sttspL'nsions. and vari<Hts phar(cid:173)
`maceutical solutions. Bridlv. /a/J/1'/s are solid
`dosage forms prep:tred bv compression or mold(cid:173)
`tllg and contain medicinal substances with or
`w tthout suitable diluents. disintegr:lllts. coat(cid:173)
`ings. colorants. and other pltannaceutical ad(cid:173)
`.itmcts.
`l)ihtents arc IIL'L'L'ssary
`in preparing
`tablets of the proper size and consistcllc\.
`Disintcgr:mts arc ttscd when rapid separation of
`thl' tablet's compressed inl!,redicnts is desired.
`This insures prompt exposurP of drug particles
`to thL· dissolution process tltcrehv enha11cing
`drug absorption. Tablet coatings are of sevL·ral
`t vpes and for several d ill'cn'nt purposes. Some
`called entl'ric cuatill.4-' are employed to permit
`safe passage of a tablet through the arid cnvi(cid:173)
`ronnH·nt of the stomach where certain dntgs
`mav be destroyed to the more suitable juices ol'
`the intestines where tablet dissolution safelv
`takes place. Other coatings are emplovL·d to pro(cid:173)
`tect the drug substance from the dcsLructin·
`inlluences of moisture. light. and air through(cid:173)
`out their period of storage or to conce:tl a b:td or
`hitter taste from the taste httds of a patient.
`( 'ommercial tablets. because of their distinctive
`shapes, colors. and frequently cmploved mono(cid:173)
`graphs of compa11v svmbols and dntg strengths.
`f:1cilitate iclcntilication by pt·rsons traim·d itt
`their use and ..;t•n·e as an added protection to
`public hl'alth.
`Capsull's are solid dosage for111s itt which thl'
`drug s11bstance and such :tppropriate pharma(cid:173)
`celttical adjunl'ls as lilll'rs are L'nclosed in either
`a hard or a soft "~lwll ... which is generallY colll(cid:173)
`poscd of a fonn of gelatin. Capsull's van in silL'.
`depending upon the anto1tnt of drug to be ad(cid:173)
`tninisten•cl. and are of distinctive shapes and
`colors when produced comtnL'tTiallv. Cenerallv.
`drug materials are tdcasL·d from capsull's fastL·r
`than front tablc·ts. ( 'apsuks of gelatin. a protein.
`are rapidlv disligured within tlH· l!,astrointesti
`nal tract. pcrtnitting the gastric jtticL's to pemw
`:1tt· and reach the contents.
`SllsJWII.'iions ;tn· pn'parat ions of lin<'h di(cid:173)
`\·ided drugs held itt suspensio11 throughout a
`suitahll' n·hiL·k. SttspL'llsion~ takL'll or:dlv gl'tl
`t·rallv emplov
`:111 aqttcmts
`\·elticle. wlH'l'L'as
`I hose <'lllplon•d for ot Iter purposL'S ntav 111 il i1c :1
`dill't•n•nt \<'iliL·IL-. Sitspcnsions of <·<·rt:tilt dn1gs
`
`
`
`DR. REDDY’S LABS., INC. EX. 1064 PAGE 8
`
`

`

`/)OMI.<fi' h11111' 1111tl Nu/1/l'o., uf i\diii/11/.'>II'III/<JI/
`
`.).:
`
`l'or 111
`t11 I)(' 11!-.t'd lor int raiiiiJ!-.t·ttLtr IIIJ1't'lltlll
`!-.LtiH't'. 111:1\ Ill' lll:tiiiLiint·d ;~sa sllspl'nsion i11
`:1
`s11itahlt· oil. 'lo Ill' SWiJWIIded. till' drtll!. particlt·~
`lw ill!-.olllhh· ill tlw \ l'itit·k itt \\ llicll tht•\
`11111st
`;tiT pLil'ed 1\e:trh :til stiSJH'IIsions 11111st
`I)('
`sklkt'll !Jl'ftll'l' 11!-.illg ht'l':IIISl' tilt'\ ll'lltl to Sl'tlit-.
`Tlti!-. iltSIII'l'S 1101 on I\ 1111ifortllll\ of tilt' prt'jlar:t(cid:173)
`tioll btl! lllllrl' i111port:t11t 1\ the :tdlltilli!-.t rat ion of
`till' propt•r do!-.:11.!;1'. Susp1'11sio11s an· :1 11!-.l'flll
`llll'all!-. ol' adtninistl'l"illg largl' aiiiOIIIIl!-. of solid
`diill!.!-.
`tl1at \\ottld Ill· int·otl\t'lli<'llth
`t:tkt·n in
`tal>ll't or c:tpstdl' for111. i\lso. a liqttid prt·p:tra
`t ion is IIIOIT t'IJII\'l'llit•tll to adtlliiiiSlt'l' to those
`who an· tlll:thlt· to s\\'allow t:1hlt·t!-. or cap~til1·s
`l11 :~dditio11 !-.IISJll'll!-.iotl!-. han· till' ad\':tlltag<·
`o\'l'l' !-.olid dosage f'ol'lll!-.
`ill
`th:1t till'\ an· prt·
`!-.l'Jllt•d to tltt· htllh in fill<' particlt• sl/.1'. rc:11h lor
`till' dt.'i.'ioltlllilll prm·t'!-.!-.
`illllllt'di:tll'J\ IIJlOII ad
`nlitli!-.ll':ttion. llo\\'t'\'t•r not :til oral suspcnsioll!-.
`:trc llllelldl'd to Ill' dis!-.oln·d :111d ahsorlwd II\ tilt'
`hoch. hll· installl'l'. K:1oli11 i\1ixlli1T with 1'1•t·ti11
`t'llllt:till!-. stlsJ>1'11clt•d k:tolin. :1 natural!\ lllTIIr·
`ri11g ;~dsorlwn t Jll:ttl'ri<tl. whicl1 i!-. 11sl'!'1il ill till·
`trl'atllll'lll of tharrlll':l l1\ \'irlllt' of' Its :1hilit\ to
`n•sist dissolllllllll and ahsorptio11 and rclll:till ill
`till' intestinal tr:1l'l long t'II<High to adsorb l'Xt'l'!-.(cid:173)
`si\'1' illll'stinal ll11id on the large s11rt'an· an·a of'
`ItS J>:tl'licll'S
`Drug!-. adtuinistt•rt·d i11 solt1t ion arc gctwrall\
`ahsorlll'd IIliich morc rapidlv tha11 thosl' adtnin(cid:173)
`istercd in solid fonu. siiH't' till· pron•ss of' disso(cid:173)
`lutioll is 11ot rcquirl'd. l'harmaL'l'lllical solutions
`dill'l'r in tile t\'pt• of soln·nt l'lltphl\'l'll :tiHitlll'rt'(cid:173)
`fore in thcir lluidit\ charact('ristics. S1'\nal of
`tile solutio11s fn•qtll'lltl\ administered orallv an·
`di\irs. which arc solutions ill a SW1'l'lt'IH'd ll\(cid:173)
`droalcoholit vehicle and an· ~l'IH'ralh IIIOI'l'
`tuohilto than \\'atL'I'. '>lf/'11]1.'>. \\'luch gcneralh 1111-
`litt' slllTliSl' solutiDIIS as the swcct vl'!Jiclt·
`rl'slllting in a
`,-iscD11S pr('par<ttion. ;~nd ,.,u/11-
`/tu//.'i thctust•hcs. which ollici:dlv an· prcpar:t
`tions ill \\hich the drug substallcc is dissol\'l'd
`pn·dolllill:tllth in :111 :tqU1'1His Vl'hiclt· and do not
`for rt•asons of thl'ir llll'thod of pn·par:lliOil (l'.l!, ..
`illjl'ctions which 11111st he sterili;.ecll fall i11to
`another c:ttt·~on of phanu:JL'('IItic:tl prcpara(cid:173)
`t ions.
`ABSORPTION. t\hsorption of drugs after oral
`acilninistratio11 m:l\· occur at the various both
`sill'S het\H'l'll the tnoutil and rectum. In ~en­
`era!. the higher up a drug is absorbed along till'
`length of thl' :liillH'Il tan tract. thl' more r:1pid
`will be its action. a dcsirallle fcat11re in nwst
`
`l>t'l':1ll!-.1' of till' difft'l'l'lll'<'!-.
`111Sl:11ll'I'S. Jfo\\'1'\'(•r
`till' l'lil'lllll';ti :tlld pll\-.'>IC:tl
`llaltll'l' :llliOIIl!.
`ill
`drt1g suhst:tlll'l'S a11d in till' lonlls in which thn
`:1r1· pn•st·tttcd to till· both. a l!,l\t·n dn1g 111a\ I)('
`IH'tl1'r ;tiJ!-.orl)('d fro111
`till' 1'11\'IIOillllt'lll of one
`po!-.lllllll than f'ron1 attotltt·r. IITl'~pt•ctin· of it!-.
`rcl:tti\1· lol':ttiOII \\'ith111 till' :tliii!CIIl<ll'\ tr:ll't.
`Tilt' or:tl c;l\ It\ is tlst•d on 1'1Tt:till OlT:t!-.ion!-.
`a!-. tIll' :1i>sorpt io11 Silt' for n·rtain dntg!-.. l)h\'si
`t·:tlh. tIll' m:tl :tbsorpt ion of drugs IS m:lllagt•d h\
`allo\\'lllg the dn1g sul>st:tll1'1' to h1• dissolved 1 il
`not J>l'l'St'lltcd as a sol til Ioiii and wlliilll'ld ill tilt·
`oral cavil\ with illfl'l'lj11l'lll or no swallowing
`1111til thl' tastl' of tht· drug l1:1s dissipated. This
`pr1>1'1'Ss is :tt'l'OIIIIlltHbtt•d pllarnJ;tcettticalh h\
`providtnl!. till· drug in :1 di!-.!-.Ohl'd statt· I inqu·t·g(cid:173)
`n:1tl'd on :1 cotton swal>. lor inst:tnn·l or as 1':\(cid:173)
`tn·nwh solldllt• and rapidh dissolving 111ll'():1tcd
`tal>lcl!-.. lhtlgs cap:tlllt· of hl'illg ahsorl)('d ill till'
`niOIIth 111:1\ Jll'l'Sl'lll tltt'lll.'it'h't'.S to tht• :thsorhllll!.
`Sllrf':tt'l' Ill :1 IIIlich 1110r1• l'OIICI'IIlr:lll'd f'or111 tha11
`\\·lien swallo\\Td. sint'l' drtlg!-. bt•l·onH' progn·s(cid:173)
`si\'t•h 11101'1' dillltt•cl with gastrointest in:tl Sl'LI'I'(cid:173)
`tions and l'OIIlt'llh :1s th1'\' pass :tlong thl' :tl1
`llll'lltan tract. \\'he11 tlll'st· st'lTCtions aclvcrseh
`:dl1·c·t
`till' stabilitY of a drug s11bstanct·
`its
`:1l>sorptio11
`;ts
`:til
`:ll'tive molecule IS f'nrthn
`dt'CI'l'ascd. and oral al1sorption or parenteral
`;1dministration
`111:1\
`ht·
`rctptirt•d. Sitnil:tr
`:dtt•rnativ1·s m:l\' I)(' rcquirnl lor drugs tl1at an·
`l'S!Jl'cialh S11st·t·ptil>le to llll't:tholil' degr:tcl:ttio11
`l>v thc liver. since on gastrointcsti11:d ahsorp(cid:173)
`t ion. dn1g std>.st:tlll'<'S l'lltt•r tht• portal circtlla(cid:173)
`tion and an· exposed to the detoxification proc(cid:173)
`css(•s of' the liver.
`CtiiT('Iltlv the oral or suhlinqua/ 1 beneath the
`ton gut• 1 administration of drugs is rcgularlv
`l'111plovvd for onh :1 f1·\\· dn1gs. with nitroglvc(cid:173)
`nin andu·rt:Jin steroid sex hon11oncs lwin.l!. thl'
`i>cst exa1uplcs. Nitroglvcerin. a coronary vasodi(cid:173)
`lator used in the prophvlaxis and trl':tliUellt of
`angina pectoris. is administen•d in tlw form of
`till\' t:1hlets which :liT allo\\'cd to dis.'iol\'c under
`tile tongue. prodttcing thl'r:q)('util' eff1'Cts in I to
`~ minutes after admi11istration. The dost• of ni(cid:173)
`truglvn·rin is so smalllusualh ~()() lllct!,l that if
`11 \\l'l'l' swallo\\1·d tlic restdting dilute gastroin(cid:173)
`testinal colll'l'lltratiun ma\· not r('sult in reliable
`and snliicicnt drul!, :thsorption. En·n IliOIT illl(cid:173)
`portant. howl'vcr. is the fact that nitrogl\'ccrin
`is rapidh dcstroy('d hY the liver. thereby further
`red