`22nd Edition
`
`ED
`
`"O" '" °”'EF
`.
`-
`
`CHAIRMAN or: THE BOARD
`
`Loyd V. Allen, Jr_ P]-ID‘ Fgph
`Professor Emeritus
`U '
`.
`niversity of Oklahoma School of Pharmacy;
`EdltO -' —Ch'
`v
`r '"
`lei. international Joumai of Pharmaceuycag
`Compounding
`Edmond, OK, USA
`
`Lisa A. Lawson, PharmD
`Dean and Barbara H. Korberly Professor in Women's
`Leadership and Health
`Philadelphia College of Pharmacy
`University of the Sciences in Philadelphia
`Philadelphia. PA. USA
`
`EDITORIAL Bomb
`
`Adi‘-‘b0Ye Adeiare PhD
`F’
`’
`.
`P:Ef::50T iii Pharmaceutical Sciences
`5-‘iphla College of Pharmacy
`U '
`'
`-
`.
`.
`.
`p;'_'I""-:3'tY of the Sciences in Philadelphia
`'8 elphia. PA, USA
`Sh
`D E'"'3 9- Desselle, FlPh. PhD, FAPhA
`ea” and Professor
`College of Pharmacy
`California N rm
`.
`.
`Rancho QD'%DV:taé:U3grfirsity
`"i"d"" “- F‘-‘lion. PhD
`Chair, [)apartment of Pharmaceutical Sciences
`Associate pr f
`College of P:a:::C:y0i Pharmaceutics
`U '
`.
`A|';::T:r3iq3;N£w Mexico
`
`- M, USA
`
`Depart
`
`Anthony C_ Mofiat PhD
`,
`Emeritus P
`r0fe330r of Pharmaceutical Analysis
`.
`Chemiggrint Of Pharmaceutical and Biological
`UCL School of Ph
`London, UK
`armacy
`
`eutlcsi/Drug Delivery
`
`Yvonne Perrie. PhD
`Head of Pharmacy
`Professor in Pharmac
`Aston University
`Birmingham, UK
`Nicholas G. Popovich, PhD, RPh
`Professor and Head
`Department of Pharmacy Adm
`College of Pharmacy
`University of Illinois at Chicago
`Chicago. IL, USA
`
`‘inistration
`
`ml), PhD
`tical Outcomes
`
`Kenneth M. Shermock, Phar
`Director, Center for Pharmaceu
`and Policy
`Department of Pharmacy
`The Johns Hopkins Hospital
`Baltimore, MD. USA
`Donna 3. Walt, PharrnD, FiP|'I. FASHR BCP5
`Clinical Pharmacist
`Indiana University Hospital
`Indiana University Health
`lndianapolis. IN. USA
`
`|PR2015_0-I 099
`|PR2015—01097
`
`|PR2015-01100
`|PR2015—01105
`
`University of the Sciences
`Phlladebhia
`College of
`Pharmacy
`
`'
`
`h
`London - Philadelphia Pharmaceutical Press
`_Lupin EX1177
`Page 1
`
`Page 1
`
`
`
`Published by Pharmaceutical Press
`
`is a trade mark of Pharmaceutical Press
`
`Pharmaceutical Press is the publishing division of the Floyal Pharmaceutical Society
`1 Larnbeih High Street, London SE1 ?JN. UK
`University City Science Center. 3624 Market Street, Suite 5E, Philadelphia. PA 19104. USA
`Twenty-Second Edition
`
`Copyright © 2013 University of the Sciences in Philadelphia
`ISBN 978 G 35?'11 D62 6
`ISSN [Print] 1558 2922
`ISSN [On|l'ne) 2050 645?
`
`All rights reserved. No part of this publication may be reproduced, stored in a retrieval system. or transmitted in any
`form or by any means, without the prior written permission of the copyright holder.
`
`The publisher makes no representation, express or implied, with regard to the accuracy of the inlormation contained in
`this book and cannot accept any legal responsibility or liability for any errors or emissions that may be made.
`
`Printed in Ann Arbor. Michigan. USA by Edwards Brothers Malloy
`index provided by Indexing Specialists. Hove, UK
`
`Entered according to Act of Congress. in the year 1885 by Joseph P. Remington, in the Office of the Librarian of
`Congress. at Washington DC
`
`Copyright © 1889, 189d, 1905. 1907. 1917 Joseph P. Remington
`
`Copyright © 1926, 1936 Joseph P. Fiemington Estate
`
`Copyright @ 1948. 1951 Philadelphia Coilege of Pharmacy and Science
`
`Copyright © 1956, 1960. 1965. 1970, 19T5. 1930. 1985. 1990. 1995 Philadelphia College of Pharmacy and Science
`
`Copyright ® 2000. 2006 University of the Sciences in Philadelphia
`
`Library of Congress Cataloging—in~Publication Data is availabte
`
`The use of selected monograph data from Martindale: The Complete Drug Reference (pubiished by Pharmaceuticai
`Press) is courtesy of A. Brayfieid and staff.
`
`Notr'ce—-This text is not intended to represent, nor snail it be interpreted to be. the equivaient of ore substitute tor
`the official United States Pharrnacopeia (USP) and/or the Nationai Formirlary (NF). in the event of any difference or
`discrepancy between the current ol‘fi'ciai USP or NF standards of strength. quaiihq puritgt, packaging and labeiing for
`drugs and representations of them herein, the context and effect of the officiai compendia strait prevaii.
`
`Page 2
`
`
`
`Page 3
`
`
`
`903
`
`PHARMACEUTJCAL DOSAGE FORMS: MANUFACTUFHNG AND CDMF‘OUNDi|'\|G
`
`tI'e.'-It eye Lll.‘§lJI‘tll:l't-i was limited, Et{\' was the Siillt: of
`tt:
`:tt,5,et1t.~.'
`eye tsttr}_'1er},' zttttl visitntt eerreetiutt, which \\-‘:15: Iitttitetl to eye-
`§_';l:.tssets. lli this p:t.~tt 50 years, :1 li1l)tl(.‘l‘Ii [}llEll'l11£iU()l1llU£ll it1tltt:str_V
`.~‘.peeitIli:«:it1t'; in U}'.tl1iIl‘.i{lllillL‘ prep:tt'tItitu1t~'
`ll{l.‘~i t|t:\'e|t)petl It) .mp-
`pnrt the 2I(l\-'£ll1L‘L‘!~; in (.li:.IgI'I():-ii!-i :tntl [l'L‘&I[ll1L‘Ii[ of eye (ll.‘i(J£|.\'L‘.‘-I, in
`eye stirgery, and in ermtnet lL‘|lS tlt.‘.‘a‘i£',Ii and use. l3t.‘L‘:itl.*iL:
`iii" the
`v:triet_v 01' uphthttlmie pruthtets re:Itlil_\_' 2I\r'£lil:Il)l(J t:t:mmet'ei:tli_\-',
`the plmrméleist new is rarely ]'t.'t;t,1ll'(.‘t.l tn etmtpuunti :1 pzttit.-nt’:~'
`uplttlmltttie prescription, More itltportttnt, lmwevei‘,
`is that the
`])l'mfI]'i£lCl.*if :tpp1'eei::te even .~:1t|'tt|e tiifferetteett in t'm'|ttttl:ttinn.~‘
`that niay itnpaet ei'lie:tey. etmtfurt, cnmpattihility, or rtttitniaiiity
`of ti prepttrmiott fin‘ patrtiettlttr pzttiettts.
`(lttrrentiy :l[‘iLl in the future. in ntlditinn to the zitivztneus in tins-
`zIt'~,e~i'ort1t teeltnuiogy, drtté, trtolecules will he tlesaitgnetl ztnti opti-
`ll1lZ1'.'tlb‘])t’..‘Cil'l(.‘illly t'tn't)p|tIl‘i;tltnienppliezttioti. New [l]l.']':i[]liJSl]'iil}:"
`l'JCI‘..'t>l1’.t(: ztvztilahie for preventing lllllttlticfih‘ eztttsetl l:-3,’
`tle_;';ette1'::-
`tive tlisemte —iitelutii11£-,zige-rel:ttetl mzteulztr tiegeiterzttimt (Ah-11)),
`l'l1:’l()l.lli\i' edema, and tli£ll'JCtl{.‘ t'etitmp:ttl'iy. llit)teel1|mlt)t';ie:il prud-
`uets may also heeotne zwztilalzle to treat e:tt1.°tes of ntt1ltii'ttettJt'i;Il
`eye Lli:-;ertlet':~' like glttttetttitzt. Sttelt speeiztlizetl tlterztpetttie itgettts
`also will require e.'t:'et’uily tl{:Sli,"_IiL.‘Ll mttl (:0l1tp2ltil)le tlnsztge fut‘n1.~;_
`l,’ut-J(.‘:.tl.l:-it.‘
`tl<>:~':I£~,e t'm'ms are iztshionetl to enmplement the re-
`quire-me21t.~: of the tl1{:l':l[)cttti(: :ti_';e11t.. and the izttter are selected
`for their ltctitnl tlptm pztrtieular tiS.*illt.:.'~' so as to inotiify ti];-tr
`ftn'tetim1, we will tmw turn us att|c:ie1'i|)tir>t1uftiettlartissttes;Int|
`their pltysitalttgy.
`
`ANATOM AND PHYSIOLOG OF THE EYE
`
`titan)’ \VEl_\’5 the httm:tt1 eye tr} tm ideal UI'9_:lIl for sttttlyittt;
`lit
`tlrttié,
`(i.t'.ll1lllllSU':I[lt)l‘l and tliRt)t)>:itit)It.
`f_>l‘}3,:lIl
`p|1_\'si<>l0t'»__\-‘,
`tttttl
`l.l1]lt.‘llt}I1.
`llnlilte Fllflll)’
`l‘.*tltlll}' urt"_:-tits.
`II'|U.‘il
`til‘
`iii!-4
`.~ttrttet1tre
`ezttt he ittspeetetl willmttt sttngieztl
`itltervetttiurl.
`its m:teI'(:—
`.‘\‘(.'{J[IlL' rextitatises L‘£Il‘I he ittvestitizttetl
`h_\r direct til)!-iCI'\’(ifi(Il1.
`its ttlirziettltitts i'ttt1t:timt, st)
`intt'ie::tt: and etm1ple.\',
`t::J1tvert-
`int‘,
`:1 ]‘tl1_\'sie:tl
`l.'l(:tJIrllI'Il{lL'{l‘iCiIl(: stimttltts into :1 ehemiettl sig-
`nal that is eettpletl
`to tlitttattt 1](:lll‘l)[i.'~' for sigttttl pmet-:.~a:-;i11.t.‘_
`by an eleetrneltettlieztl wave. is (lt.'iLOCt£llJll..‘ hy settsitive lIi.\'[l‘l1-
`mt.-nts ztttaeitetl to external iIiS.'\'tIt:h'. ’l‘|te imraira fer the |ll||1Ufl0|'l
`anti [m_tteeti:1tt nf this illlpti-I'i£lIl|I [)l‘}.3,Elli that limits ltttmzttts to
`
`is the ll!-i:x'llt:h t_‘tJtll]}lL"illl1-l- ll‘ The
`their L'.\'I(:l'I'i(Il L‘l'l\'il‘lJIli1'I(:lll
`$ii‘i.lI.:[l.Ii‘L‘.‘i to he t.lU.'~'U|'ll1t_‘(l tire llli.l.‘w'l|‘EIIL’tl
`in |‘i,£,lll'<-'3“ “'1 Hi
`-13-}.
`I"i}_'»,tiI‘e -i.i—l prm-'itie.\'
`:I
`liI‘}|‘1‘/,tti|]'_;]l §t_1;['|r)!i. iii the '-'.""_'b"l];
`itletttii'_\'i1t£_ the Il'l£I_i(Jl’ .~'t1'tIet11re:-;
`i|I]|_l tlieir l|llt_‘!'i't.'l!IIltliifiliillfi-"
`[“i,*.".lt|'t;.~t -ifi-'_ ~eltm\'.~< in }.'*.t'e:Itet' l.l(.'[£Ill the .'t|1turiut‘ i"ml'm “l :1“:
`eye :tntl t_‘_VL‘li(l.\',
`in \'t.'I‘fl(.'itl seetitm. etttpltztsizittil >“’“w "1 “IL
`!~‘t:'ttett1re:»'
`:I.‘i!~‘I)Cl€Ii'.t.'Ll with te:tr :t1}|):lt':IllIH." 1"'li.".1I1‘L‘ —l.l_~-l
`"‘_'.u_H-
`|’1li:|.\'l7.<:S the ilnwnftetI1':s into the I1:IStll S-[I'tIt:lllI't_‘3-i." This lJIlLI
`iittrntittetimt will fuetts (Ill the £IIl:iitIIl‘ilt.':il xtrttetttres t:t:~li1]3U5"'
`ill}; the eye :t|1tl their l'ttnetitm_
`
`EYELIDS
`Ifiyelitlat serve [Wt] ptii'puse.~:: mt.-el1;utie:t| pruteetimt tll’1l"~‘-f1l“h_c
`zmtl et'eattit>t1 mi’ :11] tlplltiililii milieu For the (.'(Jl'1]L‘(I.
`'|‘he n1ni:|:
`stlrftteex tit‘ t'|te t.:‘\-‘£.'lll.lb‘ itlltl the utttt-:t't1m:<t
`:tt1t'i':tee:~‘ oi the 03;‘
`(1i'Cl1ll)I'lUiii.ULll3)-’ the te;t1‘:~', It etittipmtite of at-eeretinll-.‘i l"'”"' I)”:
`l{l(.‘l'li‘ti;Il _t';|:intls ztntl sepeeinlizetl cells resitliitig in limit the lmili-ic
`ienverinti, the _~;e|er:t} and pziipehml tum-'t.-rim: the inner Hllflilg-1
`of the lids] e:mjtttteti\':t. The :tItteeh:tIIt|1er li:l.H'- the ::l‘si1i'’‘'' “ '
`I'I:Il'l'(J\\-' eleit (ll't't.'Ctl_\' I)\’CI' the I'm1tt ml‘ the evelmll, with l“""|l‘cE’l
`like (:.\‘U.:l1.‘ii()t'I:-i t|pw:trtl nntl tlt>wt1w:tt't|. The ptteltetsa tire e:tl|Lt
`the .~¢1tperim' :ll1(l tuft.-rim" |'rn-nier.-.~< tv:ttti1.~:), and the entire 5i7“““L:
`the et>t1_itIt1t:riv:tl L'lIl-tlt:-H:lL’. The elliptienl tipeni:t_:1;ht.-tween t 3“;
`eyelitis is enlluti the p:1lpei:i':t| it-csttru.-.:ii1ti the corner uitlie I-"3""
`wlte-re the e_\_'elitl.~' meet are the enutlti.
`
`OVERVIEW OF STRUCTURE AND
`FUNCTION OF THE EYEBALL
`Structure
`
`farm
`:-:1
`.
`'
`The t-:_\*eh;t|i is lmtt:-tetl in the htmes till the 3-iliilll, iuitteti to I
`H
`mt
`:tttp1'n.\'itn:Itt:l).-‘
`t!_\-'
`'I'iIiiltl--5li:I]'tt.'t.l
`ltntt.~‘it1_L'>,
`fur
`the I-'.\"-'
`_}
`Uillltxtl the nrhit. The \\-':1ll
`rat the llttntztit eve-|::1l1 ilttiihliri. :1"-l"'|“,'
`is i..'UIIi|l(1h‘L'v‘.l oi’ tliree L't>Iit.‘l:II[I'i(.'
`l(I\‘Ci'.'-i that l.‘lI\'t..'l(i]1 Ill“ ll”
`ttiitl lt_'1illL‘IIl£lI' (_!UI'(.'.;''’
`'
`
`1’H J"! T-I R H Bitf H lb‘ i'..-I i’i"lR
`The uttter 3-:t:lL‘I‘.(Il
`|:t}'t:r is tang]; mm i,|i;l|,]L- hm uni)’ -‘ill-lllllhj
`elnstie. The tintt.-rim‘ ll]ll'tl is etweretl h\-' the et>|1itmeti\*:!. 5' Ulufil:
`tr:I1t:ip:u'i.'ttt. nltteutts :<tIri‘:tt.-e. The ITIU-.*-;[
`:!.]Il'l,1l'lll)I'
`|'Jt1I‘[l.l'.|Ii Of {Ila
`miter |:I_ver
`l'm‘m:-: the enrttezt,
`:l
`.‘il.I‘t1t.'tlli'L' so |'t:;_i_tt|:It‘ and T‘
`
`Pupiliary sphincter
`muscle
`
`Iris
`
`Anterior
`chamber
`
`Epithelium
`P1
`
`Bowman's
`membrane
`
`Stroma -—
`
`Dest;emet‘s
`membrane
`
`Endoihelium
`
`Lateral recius muscle
`
`Sclera
`
`Fovea tzentraiis
`
`Optic disk
`
`Central retinal BT13”
`
`Posterior
`chamber
`
`Trabecular
`mashwork
`
`x Medial recius muscle
`
`HEN“: 4_5_ L _~,_ wm“.”_\. ll“,-;',1i;i1t:tlmtruuiiuii the c,V§|t;tIl, :|ltt.~.tt:tt1ttp, the iIii[)r".m”l M mmm m_”C“m_$ “mi 1|,,_.'..- ‘mg._.rm|;.[inm:l1ip}: tlt:t.L‘.t.i?:r
`,_.”“_.|-_ “K. [j,”._.,-ml;
`i,-._-_L-in r;| [ht tn: []t.‘I .IIL illll.‘-iI.|IL.tl In the Ill.:IL[IlIllL.Ll \ tut. I{t.|.ItJ-.t _«.wt..~. .m_ .'st1gt;i;g,n\-{_- "mi .1“. pmpm.[im,‘.l|.
`IIIL Ll1«‘”'
`H |H”!,_L....__,__..l.[_.f,;,]t
`,'_._!1{_.,.._-.-;.J]t-_-gliglitlt -_';re;‘.iIt-rillsiii rim: l|if..'li. ii.ntt:'ter4}'..\letuti l..‘ilItrI‘:|{ri|'|L',\:_ lug” ism. \\!”n|L TX’
`
`Page 4
`
`Page 4
`
`
`
`Glands ol_
`Krause
`Conjunclival T}"
`Cenjunclivasac
`
`Wolfring'5
`glands
`
`Crypts of
`Henle
`
`Meibomian
`
`glands
`
`Glands of
`Zeis
`{Sebat:eous)
`
`“Glands of Mull
`(Sweat)
`
`Glands of
`Manz
`
`Vitreous
`humor
`
`-vv' " "ll
`..-'..
`‘
`'
`-
`rs
`-
`I he ITUIII hull of the eye. in \E..I[II..:Il>-{..L.tIt)I1.IIl.lLIlIll;}1R‘-lL
`Figure 43.2,
`[lie impnrtzuli s11"tIetlII'e.~i
`:I.‘-i."»<IL.'l:ll.'{.‘tl \\'ill1.e::rne:I and the lrlitll 0 I “-
`i—'_\’e. l!1L‘lt1tliIl;.l, the eyelitls aim! the t.‘-,lant|sttssnemtetl\\'1ll1IU-lFN-
`
`Lacrimal sac\Plica
`
`Inferior lacrimal punctum
`inferior Iacrimal canaliculus
`
`/"Valve" of Hasner
`(Laerimal plical
`
`Inferior concha
`
`Figure. 43-‘-3_ 1‘h,_. 5“-“¢_-1'[|r(:1< ;t,~::.'ltt:i;I|L'l.l with the te:II’!~i :Iml 1;tet'in::il
`lrnw ;1m|
`;.L-;_-._n5g.- it: the n::st:l.'terim:Il s}‘>ileII1.
`
`tt':tust1:t1'—
`water eentent so e:u'ei'ttlly ittljustetl that it ztets as :|
`em wintlnw. It is tlevuitl ul hluetl vessels. Over the I'ettt:Ii11int'-_
`two thittls til" the t’-_lehe. tlte lllirmts e<>ll:t_t_'r,eit—t'ielt emit is np:tt|11e
`tthe white ml‘ the eye) and is eztlletl the selem. It eunt:Iins the
`"lli-‘I'0eireulzltitm, whieh nuttrisltes the tissues nl' this :tuIeri:)r
`
`OPHTl-l.1\Ll'v'llC PREPARATIONS
`
`909
`
`setlnlent. zuttl is ustt:|ll_\' white except when irritated vessels he-
`enme tlilntetl.
`
`thicker than the selertt and mug-
`sli,t§htl_\'
`The t,-m'ne:t,
`intl in thieltness l‘|'t)m Sill) ntiermneters tr:
`1 mm, eeltsists til‘
`[‘“.-._-
`i;_|¢_-miliultle l&I_\'eI's.
`l’meeet|itt_£_ l’rr.nn the most zmteriur
`l{l}’t_'I', these are the lt}'tlrnpht:hie stmtifietl sqtttttttetts epithe-
`lium, which is l.1IIt.lt:I'lEllLl
`h_v the l’.«.>wm:m rnemlarzute, then
`the stttmtu :1I:tl
`the lleseetttet ]l‘|L‘IlIlJ]'£li‘iI‘..‘. zuttl then the in-
`IteI'tu0st layer, the entletltelitutt. The strnmtt is :1 lwtlrnpltilie
`eltlslie ttetwurlt of l1it3,l1l_\' m':E_:u1izetl etsttttetrtive tissue and is
`the Il‘IlL‘lit.'St
`l:t_ver nf the earnest.
`'l‘he filtmtts enllztgemrieh
`Ileseetuel Ittemlmllte sep:|t':tles the strum:I l't'0t1l
`the single
`_~tt|u;u11utt.~;—eell l:t_ve1‘ til‘ endethelitntt. the leetltitm of tlte pump
`that keeps the L‘-‘J1'l]l..‘:t in its t‘el:Iti\‘el_\‘ tli.-.‘l1}’tl[‘ilIiJf.l, tr:tnsp:lr—
`ettt state. The enriteu ftlnetiutls as :1 hil;|_t'er httrrier. with the
`ll‘\-‘Lll't}pl‘I()l}l{.‘ epithelittnt us the prit1I:t|'_\'h:trt‘ieI' to ll}-'tl]‘t}]".|l]ill(.!
`ntnleeules fllltl the lI_\'tll'f)plllliC stt'u1u:1 as the pt'im:u'}' httrrier
`tn lL\’{ll't)|1lltJl)it: mtileettles. .-\ seltemtltie tlt':t\\'iI1t§ of the em'ne.'t
`is pruvitletl in l“i;.‘~,m'e «Li-I nntl its relation [ta utl1L'!' anterior
`tissues in |"igure 4;‘--2.
`
`i'tHI)l')l',lu' ‘ll-tt‘a‘U[lL.-I R L.=\l"h.R
`
`The middle wtsettlar layer. or uvea. pmvitles nnitrislitttent tn
`the e_\-'e zmtl ennsists {fmm the lmelt iii‘ the eye to the frunt} of
`the ehnruitl. the (:lli:Il'_\'
`l)fJLl_\'. :II]tl the iris. '|‘he elmmitl eon-
`sists til :1 pi_l_l{l‘1'tI.-.’1ll.I._’t.l vttsettlzlr l:I_\-‘er. et)lm'etl hy 1uel:ume}'tes
`untl ll‘2IVL’I‘S(.'tl by metlit1m—sl;I.e{l arteries £I!'It.l veins, with the
`el1tu‘it}e:ipill:t|'is euntainitlti El
`ttettvnrlt of small vessels that
`nourish the neural retimt. The eiliztry Imdy emttziins muscles
`(hut etnttml
`the extensitut of the lens. ztllt.>witu_5,
`\'istI:tl ae-
`Cl)!‘lIi‘{'lUtltlLlt}l1_. as well as the eili:tr_v processes that secrete
`aqtterms ltttmor into the posterior ehuutlter tn ntztintziin the
`ititrtioettlttt‘ p1‘esstt1‘e (I()l’l that,
`in turn, lteeps the eyeltall
`full_\' expzIutle.tl. The txititttetttetl
`iris is El
`l'i[],t.‘, of ntttsettltir
`tissue ;1r:iu|1t| the pupil,
`El mtuttl eelttrie hole th:tt §l(:[h' us
`a mriztltle aperture to tJt)ll(t‘l)l pupil I.ll{1Il‘lClt.'l" nntl,
`thet'eh_v,
`the level
`til" litiht entering the eye. Tlte emtztl of h‘eh|entm,
`title of the iIu|m1'l'.'tItt pzttlts for mttlluw til the :tt|tteuus hunter,
`resides in the :tny_‘;le uf the iris. llruelfs Ittemhrtttte sejtumtes
`the ehemitl frtuu the retina.
`
`.'\'Iu‘UR.-U. Rl:"l‘l'.V'zi
`
`is :I eumplex tissue that
`This innermost l:I}’e1' of the eyeball
`sttttpurts the lI£It'\’t.'S[ll]_L", ul' ligltt
`tllrnttgilt the ettlleetive ttetitm
`of pltuttu‘et:eptut‘.~; :IIu.l nerve eells speeizllizetl for tllfillllfllllfilllllfl
`white frtutt lllilcli lrutls) er I'ur tlisee1'itit1;_'-, eule-r letutesl. ht :Itl—
`tlitiuu, the I'(.‘T.ll]fl etnlsists of eells that sttppnrt mettlltolism llilte
`the lle:t\'il_\' pitimentetl retinal
`iaigiiiettteti epithelium. which
`ptnjtges pl]-‘ltI):‘I.:t.'t:|1lIJl'.'-i of spent nmleeules untl n1et:tlm|ites,:mtl
`1'e,t‘,et1er:ttes the et's—reti|1:tl), pmvitle strttetttre [:tst1't)e_\'tes and
`I\'1illlUI' Ctlll-‘il. ur t:tJI1'frll)t1lL(.‘
`tn the primstry ftittetieit of plumm-
`tleteetittttlsigtuil
`|1rt:ees,~‘»i!1t': (the _t.5,:I1t_9,|ien eells that hr.-_t‘;in
`tn
`mtaeess the eleetmehemieal inl'r.:rm:tti<'.-it tmnsmittetl from the
`pllt)[tJt‘t:t:t.'ptl)rs)_
`
`(JO! "L;-1R (}()R.l:I
`
`Within the _t_‘,luhe, the er_vst:tlIine lens spmts the htte1‘ierllttitl—
`illletl eenter eluse to the iris and is tnieheretl h_\‘ zunule filters
`to the t.‘ill£Il‘_\'
`|mtl_\'. The lens is emnpttsetl of st
`:~llIl,t‘,lI.’
`lziyet‘ of
`I'eplie:ttin;_'r, epitltelinl eells that, with :n_5,e, flatten into layers of
`lm1;_i,, thin erystztlliite-hlletl lznuellm‘ filters. The lens is the only
`tissue in the hotly that retains all eells ever prutlueetl. a fact that
`eontrihtttes tn ;t,t?,e-relntetl nlterzttimts in size. elutity. tutti exten-
`sihilit_\‘. A [lJl1_El1. thin tI‘:IItsp:|t'ent |!1|.'i'l]l'It'El1'lC enlletl the ettpsule
`envers the nuterntest layer of the lens.
`The .’l.t{l.IL‘()HS zlntl
`\'il't'etnls ltunlurs are ittterpusetl hetween
`the snlitl stt‘t1ettII‘es of the eye. The elem‘. lluitl €I(|1l(.‘t}tlS
`ltuntor
`fills the glrilte zlnteriur tn the lens and is [1l'ill1:l]'ll)’ restmrlsililc
`fur Itutilttttiniugi etu‘reet
`l{)l’_ The gel-lilte \-‘itreous ll1lll1{)l' ae-
`Q(]|_j]'|[5 fin’ .11.-.;_~;t of the weight of the eye and resides pnsterim in
`the lens, in tlireet et>:tt.'|et with the retilléh
`
`Page 5
`
`Page 5
`
`
`
`’l‘l1e eyeball hiinses the nptiezil apparatus that eaiises the ter-
`mtitien ran the netiral retina of inverletl. Tcdllced "mil-l-95 ‘ll ll“-'
`outside world.
`
`Dimensional Stability
`DI.-li'l£.\'HI():\'.-ii‘. .s'i'. 'ii':’l‘J.l"i"}'
`
`The optical funetioii oi" the eye etills for stahility of its diiiie-ii-
`,,‘i[,n,,-_ wmuh 3,; p.~W5d._-ti ptirtly by the tihmus miter emit ‘nut
`more effectively by the iiitrzi ocular pressiire {i()l’}. which ex-
`eeeds the pressure prevziilitig in the stirrnmitlinié, tissues. This
`10]) is the 1-esttlt of ti stead)’ ]’}l'(JLlU.{."tlU1'I
`til speeihe lltiitl, the
`(l(lue{)l[§ lmmor, which iirigiitates [mm the eiliary processes
`anterior to the lens and exits the eye by an intricate systein
`of otttilew eliannels. The resistance eneiiunteretl dtirinti, this
`pzisszige antl the rate of :.ii.|tie(Jt.is prntlttetieii are the principal
`factors deteniiiiiinié, the level of the 101’. In :l(lt‘.ll[lt>l‘l to this hy-
`(.ll‘{)['1]I.'t:ll:l1'Il(.2tll l’tii'ietit>n, the aqtietms humnr aets as :1 L‘al‘I'l-1:!‘ iii
`ntitrieiits, stilistuites, and metabolites fur the tivasettlar tissues
`til’ the eye.l"
`
`PHARMACEUTICAL DOSAGE FORMS: MANUFACTUFHNG AND COlv1POUNDlNG
`910
`glauetiiiiaj; the presence of seat’ tissue Line in injury iii‘ iiil'ee—
`FUNCTION
`tien; or tlelieieiiey of tixygeti or excess l1\.L]m[imf‘ 51.9]; as may
`eeetir diirititi, the wetii‘ini.'; of lI]I|)['t}pi_-_g}'l‘\; |'1”(_-L] co1‘it:1et
`lenses.
`A wmtittl oi the L‘UI‘l1I::I may heal as an npatiue pateli lllill ean
`he a pei'iiianent iiiiptiirnieiit til visimi unless it is l(!tJ:ll.l.'lli iii the
`petiphe1'y of the euriieti.
`The enrnetil iierves do not supply all fiirnis of setis:itit:ii tn
`the eiiriiea, hut pain and eiiltl are well supplied. The pain i‘ihei‘s
`have ti very ltIW thi‘eshtili.l, which i']‘l:tlit.:,\t the t;omt_-ti tine til I110
`most sensitive areas on the surltiee til’ the l‘H)L[\i_ |t new is titjgreetl
`that the e<ii'nt-.-:i possesses :1 ti'1ie sense til l.lJlll..'l1'.
`i1t_..-W cmlii-.;}_s
`supplyiiiti, the seiisatieii of heat appear ll) he l:ieltin:1.
`Tlie eiiriieal epithelium pmvitles :in ellieit,-m la:m-ier aiiziillfil
`haeterial
`iiivzisiuii. Unless its eiyzitiiiiiity has heen hmlieii
`I15’
`an alirasiun iii triiuimitie fJ|)(:IIll‘l}:’, iii‘ deft.-et in the epitlieliitml.
`l35lll10§31‘~'1ll'3 liilct‘-Wlil. H5 il Ttlle, etiniitit i.5_:ii1i a leet|1<:ltl_ ’!'t':iniii:I.
`tl'iei'efnre, plays an iinpnrtaiii part in most til" the iiileeiiiitis dis-
`eases til the etiriiea that l)I.‘t.'l.ll‘CX(l!lI:I1(JllSl\*, A iiieaiis til detect-
`mg :ilir:isii>i1s en the em-neal sin-fziee is al'liii't|ei.l hy staiiiiii§.':tl1U
`e-iii'ne:i with siitlitiiit l'luI>reseein. Any L,-(,1-"cal ninflsmn is 511]).
`jeet tn iiileetien.
`As with the etarnezi, any ehaiige iii the ti‘;ii1sp:ii'ei‘ie\' of tilt.‘
`lens as :1 result of :i_i_'=_e 0]’ disease can sii.itiilie:iiii|\' allleet Vifilléll
`eltirity. Less of llexil:-ilit_v til‘ the letis e:iii retliiee iristittl aee(iiii-
`nititlatitiii and eatise tliffieiilty iii ftietisiiiy;-_ nu “Cm. ”|m_.L.m_ A11‘-¢;_
`tipnn at5,iiii§,er :is a result of ii‘:itim:i, the lens may i_i_i_-nerzite i>p:ie-
`ities eausetl Iiy tl'ie usidzititiii and emsslitiltiiit‘; cit" lens prnteiiis.
`When eattiraet stiitzery is reiiuiretl U) restore elaritv in elmid,\'
`vision. the i'i:ltin':il lens is l‘L‘l'IltW't:tl and replzieetl hv -an :ii'iil'ieitil
`one. The ettpstile,
`lltlnlflll,
`is preservetl St) that it etiil ]ll'(]\’ltlt.‘
`settfliiltliiiij, for the iittphintetl synthetie ll‘lII'EIl]CLll£||t ‘elm
`
`oi»*i'it:,i i. I’.-\'i‘Hll}'i‘l’
`
`The optical ptitliwzly eensists, in setitieiiee, til the preeeriiezll
`tear hint. the eiirtiea, the tiqtteiitis liiiiittir, the pupil, the crys-
`talline lens, the vitretins Iitnnur, and the retina. The chief re-
`l'i':ietit)ti til light liar the eye iieetirs at the initer siirfiiee of the
`euriiezi, where the index of ret’raetiuii eliaiiees from that of air
`(1.00) to that til" preeeriiezil stihstaiiee (1.38). After traversinij,
`the enrltea, liglit passes tlimtigli the Ulcilfilt|l.lt:t)llHlll1i‘I'l(ll‘ to the
`pupil, where the :l[1l.tJ11I‘|[ of liizltt eiiteriiii; ilie eye is retiiilzited
`by the ptipillary tliztiileter, and to the seeeiitl relrzietive element
`ol’ the eye, the lens, wliiise variable liieail leiigtli allows nhjeets
`hoth near and far to he Iuroiiglit iiite fiieits l:ieet>ritmud:ititan).
`The shape (ii the lens, etmtmlled hy the itniseles of the eiliary
`Iietly, i'el'i‘aets and fiieiises the reduced inverted iinage ml the
`retina. Thzit inizige is sharp and clear, in part heeanse efthe high
`trtlnspzlreney tit" the vitreeiis huittnr, whieh, heetlttse of its gel-
`lilte state, keeps debris and eells lruni eiitei'in,t_'; the pathway for
`the lii_3_l'it_ The ii1i:i,i_‘-_e ftirtnetl hy the eleetrtiliizignetie light sigiitil
`tin the neural retina is eiiiwertetl to at elieinieal signal, eliaiit__‘,—
`iiig' eis-retititil tn .tir'ti.ris- retiitzil. which in turn is processed h}:
`netirzil eells into an eleetrneheniieiil sigznal ti':ins~pni‘tetl tltrtitigli
`axons to eentrail nerve cell lacidies. (.li)t'itint1nLis mainteiitinee
`of the phiitt)i'eeepI.ni's and neural tissues in a stale eapalile til
`stippiirtiiiti, the ennversinii of the exeitatinn assneitlted with El
`retinal initige tn prneesszilile iiifnrinatirin is intet},i'al tn the fune-
`tiniiiitté, of the retina and is the i‘e:tsoii retinal tissue is tininiig
`tlte must rapidly l‘I'Il.‘{8l‘I(‘.|ll?’.lt'I9, tissties iii tlte liody, The depen-
`dence of the neitrtil retina tin the inettihtilie stippm-t prm,-i([u]
`hy the untlei'lyi1iij_ eell layer, the retinal pigiiieitted epitlielittitl,
`explains why tlztttttlge to the tissue—sueh as (l(3l€l(:l"In‘lt-:t1l, 0f the
`ret.in:i or tliiniiiishetl bleed stipp|y—ean result in nearlv irnme_
`tliate and permaneiil less til” visiiin.“
`
`'l'i.‘~i'.‘1'l."l'£.H' ilti':‘.‘a'i"fJ.\'.‘s'i'lll'.l-.‘ .l"‘t')H Ri".‘l"R.\t'.".|"l|').\'
`
`i\ny alteration in the shape er traitspttreiiey of the etmtett inter.
`leres with the lt)l'l‘]I:I'tltJ11 til :i eletir iiria_t‘;e; tliei'el'nre, any pathe-
`ltigietil process. iimvever slight, may intei'l'ere sei‘iotisly with 1|“;
`!'<:S{Jl\-'lll£'_ power ti-i' visiial It-1Jlll[_\' of the eye. 'l‘r:iiispareiie_v of the
`eeriiezi is ltlrtiely :itti'ihiitahle tr) its tiitititiizetl lziiiiintir :irr:ini;e—
`inetit ill’ eells tnitl filters, anti the tihseiiee til lil(}Ui.l vessels. The
`ntirtritil eeriiea pnssesses iiii hlntitl vessels except at the seleni-
`etirneitl juiieti-‘iii, the liitilius. 'l‘l'ie eiirite:l riltist tltereftiie derive
`its tllll'l'l[llJlI hy tliffiisinii and must have eertain periiieahility
`gligmietei-isties; it also l‘(.‘t..‘L:lW.-:3-i iiniirisliiiieiit frimi the fluid eir~
`eiilatiitig tliriiiitili the eli:i:1ihei'.~; oi‘ the e_\'e and fmiii the air. ’i'liat
`mt; 1]m']]|:|l ei>i'iie:i
`is I.ll.'\'l>lLl of hlnnd vessels is an iiiiperiziiit
`t”e:1ttii'r_- iii siirtiieal _t':i‘:il'iiiit':.
`_
`‘
`l.:i”“dim___“ M‘ [hp L..,,-me. m;._i- neeiir as :1 result nl disease
`_
`.
`.
`-
`.
`-
`1
`‘:ih'(3t,‘l‘lit,'tl\\’l'(ll
`{mg I L__\‘.L_,____‘_.‘. :,1,_._\_.1m._.,,, ftp L_ttl..i||, .i s_\i1lpt:ii i
`(I
`.
`
`Lacrimal System
`The eiiiijtttieiivzil and etiriiezil siti‘l'aees are eiweretl and lt|l‘iI'l‘
`eatetl h_\'
`ti preenrneal Ieai‘ lihii. :i lhiitl seeretetl IN the e<ii1jtiiie-
`tival and l:iei'im:il g1l:l!‘lLl.N‘.“ The clear, watery st;‘t_-1-._-git," at‘ the
`lEltL]'l|'ll£ll
`t_5_l£lIlLl, delivered tliriitiiili ti Il'tl]lll)l.)l"I)l' I-inc tluctfi him
`the (:()l'l_lllI'lL‘il\-'1Illt:-]'IllK, eiiiittlins iiiiiiiemtis salts, £',ll.lU{JSIJ.l)[l1L3r
`iirgiinie eiinipntiiitls, and zip-prexiiiizitely ll.7 pereent prnti.-iii. iii-
`eltitlint‘-, the enzyme lysmtyiiie. Siiiall :ieeess:>i‘v |aei'ii1i:1l;.‘_|aii-zls
`are sittiatetl in the eetijittieiivzil fi:ri'iiees. The tear filtii, ennip:ii-
`il:-le with huth £l(|l.IL‘(Jl!S and lipid uplitlialiiiie preparaitiuiis, is
`ciinipnsetl of a thin miter lipid layer, a thielter mitliile ziqiieiiiis
`layer, and a thin inner iiuieeitl layer. it is 1'I_-nt;\\:g_-(J du]'i[]L'{l)lit1li-
`im; and, when hliiiltiiig is stippi'essed, may tlrv iii p:itelie.~;.
`It
`seeiiis [0 he tiiialleetetl hy the titltlitiuii of etiiieeiimiiiliiis iii up
`to 2 pereeiit stitlitiiit L’lll(ll‘ltlI.: to CUI'I_lll[1(.‘lIi\":ll lliiitl. i\ pll helnw
`41] or tllmve ‘).ll eatises tleriiiigeiiieiit til the liliti. The lilni til"
`feets the meveiiteiit til" emii:iet lenses and forms more easily’ 0“
`hytlrtipliilie than Ull. liytlitipliiihie prtistlieses,
`The iniiermnst nitiein prtiteitt layer of the Iilm is e.~;peeiall_\-'
`iinpm-taiit in niziiiittiiiiitie, the staliility of the Film and is |‘Jt}E-illl-
`latetl to he held in pltlet.‘ l7? ll“! miL‘rtJ\'illi til’ the eiirneal epithe-
`lial cells. Hehaeeeiis iiieihtiiniaii ti,l:inds til" the ex-elids seerete an
`oily lluid that ltJi'nis the ntttei‘ ltiyer til" the tears, helps to pre-
`vent overfltiw at the lid i1i:ir_t",iii, tiiitl retltlees t-_»\»;mm«;u_itm frniii
`the exposed Hllrlltitill.‘-I til the e_\«'e.
`Siitiiitziiietitis l)lii1ltii1t'-_ i'eplenislies the lhlitl film hy piisltiiiif,
`il thin layer til" lllll(l ahead til the lid iii:irt'-_iiis as thev eniite U!’
`tietlier. The exeess tliiitl
`is tlireetetl into the lzieiiinal
`|:ilte-—fl
`small. tri:u'tti,til;ir area l)'itii___‘i, in the {Itlfllc l)(lllt]i;l hv the iniieriiitisl
`lmftinns of the lids. The skin of the eyelids is the tliinnesi in tl‘il-'
`l"“_’¢l)'i1|1lllUlLls easily, thus pernilttinti, r:ipii.l Up<.'I'Il|1,l.5,tl|1tlUlilfilllg
`"l ll“? l’“lPUll!‘=ll fisstires, ;ii velueiiies nf ti."-its iii eeiiiiineters PW
`Slwotttl. The ninveiiieiit iif the evelitls iiieliitles ii
`ii:iri‘:iwii'I,l,", Ill
`:'l:j:'ll’fllll“l‘r‘ll l:“‘““_‘-“"~'-’“ ill 31'/nl]3[3C|'-'lll{L‘flctlflll t"i'riiii l:1l'(.‘l‘;ll in ine—
`«.
`t..ii1_tlius.
`Ihis aids ti'anspt,~i-t tn‘ |]l{:tV[_:[1I|._'I]I_ of thiitl ttiward
`tl1C‘l?lCrii‘ri:il lake and Ltlliflillilliltill of iiiiwaiited (.‘(Jt'II:lI1‘ill'|£Il1lS.
`'le:ii's are draiiietl i'ri>i1i the hierimal lalte t|ii'ntie,li two small
`t}]}l'.'ll.lIlL‘,.‘-l,
`the stiperinr and interior puneta, which drain
`into etiiiiieetiiig small
`tubes,
`the l:ie..im"| L_““”|icu[t_ wi11t_-[1
`
`Page 6
`
`Page 6
`
`
`
`thetitselvcs join at the eomnion eanaliculus that leatls into the
`upper part of the nasolaerimal duct,
`the heginnmg oi wlut,-it
`is the laerlmal sae. as sliown In l‘lg‘,I.1rt: -13-3.
`lhe Ll!‘illl'la£Et3 of
`tears into the nose does not tlepentl merely 0'1 i-lT“Vl'lY- “Hid
`enters anti passes tlltltlif, the laerimal eanaliettli hv capillary ae-
`Ii,-J”. ;m[,__.d by ;._t.‘[)ll'I.![itJl1 t‘esultiin1l'ron1 contractioil of nnlsolcs
`¢;.11I);-Llduti in the eyelids, antl lay peristalsis III the muscles near
`the e'n1alic-uli. When the lids close. as in hlinltinil. <—“1'I“l'“0l1‘”1
`ol the muscle causes tlilatation oi‘ the upper part ol the laernnal
`we and eompression of its lower portion. 'l‘caI'5 5|-"'l"|ri1[‘v'¢l ml”
`the “L. .1,-¢._. fm-L-¢.,-d down the |1aso|aeI'it1ial tltlet toward its open-
`ing: into the nose. As the lids Open, the muscle relaxes. 'l'l1e UP-
`pcr [rtrt of the sac ill-1;:l1 collapses and forces llllitl lmfl ll‘-'1‘ l0'WUT
`l"li’I which at
`the same time is released from coii1I”'lv'~“*"l““v
`Tlnts the act of l)liIll(ll'l}_‘_ exerts a suction foreU'P1'”1P ?lC'[l"" W
`rei11t‘)’\-'iJl,L'; tears from the laeriinal lalte antl cilIPl."l"l-3 [mm mm
`um me-.1 (,"|\'l[\‘
`l,acrin1ation is intlueetl reilcsi\'el_v Irv stimula~
`non ol nerve eiitlitigs ol the Ll)t‘l3L.l or t.otl_ll“lLl'‘ ‘' Ill“ “' U‘
`is -Ihulisltetl hv anesthctization of the suriaee ol I110 93""-' “ml “Y
`tlisortlers al'l’ectins.‘, its nerve luiictioll.
`_
`Thu nm.m.l| L.u[.d¢_n;|e is maintainetl free ol patliogeiiic or-
`t.‘.:Inis:ns in part by the chetnieal action t:l'cI13Y‘1‘“—'3; """-‘l‘_“~“
`lvsovvtne which no|'mal|v tlestrov sapropllviib‘ "Ft‘.F'l”3*'“'1-“ Will‘
`A .
`._
`5
`_
`--
`‘
`I
`'
`'
`‘
`’
`\
`‘
`.
`_
`limiu,-t[ action a}.i,a1nst patl1ogens,.|nt| In part In the continuous
`)l1V<§i(_}'1l flow of normallv sterile secretions. Much mmtmmy
`tvgsil [in hlclerpl
`‘hm Em;
`-m.-rur front the eve tlown i11to the
`L.
`.,
`H
`..,
`(_
`._
`_
`11 1st.
`In Lt.rt'Iill tll‘s't‘.'3’i‘i'3‘5 or UD0" all-’,i=11i. T119 l='°""“"l t‘3l‘”“l- 1"”
`.
`.
`.
`,
`. «
`_
`-
`-
`=ol
`t
`1,
`f:-1l1{;1'_Ql:t:](lt!ll{Il'P-sfFlI{.,IT.]lt}.!sI11 thelitltl)’,I't1¢l}'T.lll(JLI‘g(Jll'l\.‘ it
`to] .
`with the result that the lacritnal fluid becomes seanf_V'- {*ll‘"‘l-’.*33*
`x
`‘l’
`I‘
`I
`‘ _
`‘-
`_
`‘
`in U
`."iunLuti\.rqI g1;m.,l«; m'tv l{.“lLl to alteration in the charac-
`f
`' ll ‘he seet'etitn1 so that qtialitv as \\’<-Ill Flt‘ ¢lW1m'[.V'
`'-‘l “v’?"'-‘‘
`U H I
`thntirt11'tl This can letltl to svmptoms of dryness. burn-
`mny he
`I tli~;coml'ort and ultimatelv may ititerfefe With
`inti, antl geitera
`Visual :tetIit_\’.
`
`_
`_
`Summary
`'|‘liis in-ief overview of the structure anti tttrietititi of the U)"-’
`.
`rovitlt: a basis for tn1tlc:‘st:n1t|iI1l§'. ‘he l1I1.‘,hly mtegratctl
`should 1)
`his tniraoulous t>I'2:IIl and stttiiimil ‘'19 1m“
`tissues eotI1P“-‘ilnl-l
`I
`d
`1
`t
`_
`n no wa_v impair the
`‘ ling me ictltiolls I la I
`v.
`_
`,1 -
`_-
`|)t1:‘tant..t. t>lpr0V1i
`.
`‘
`_
`l5l'l(Jl‘]‘.l'Jl
`lun(.t1on-
`-
`-
`,
`-
`.
`-
`.,
`I
`]m|;lm_-¢ gt linietlons Ieqttiletl for m.t1mainii L
`*
`ing of the CYC-
`
`BIOAVAILABILITY
`
`THERAPEUTIC TARGETS
`|;i{,,,m5];,}-,i|i[y ofpharniaeological ttgertts is tlietatetl hy the oeu.
`I,
`_
`_
`‘mm. and p]1_V_.,-1.[,|ng__\= just discussed. lint hioava:la|n|tt_\t
`‘u M.“
`I] .
`i
`l
`=
`ilwsieal constraints anti tissue hIochem-
`film 1“ °U”_[r:.J ,(:':Ht;::]li11'tlie next sultseetions), by physicai and
`::~;tl".V Ito !l'J:}:'.,I1|:lcf’(_;riStic5 ¢,ft|1c therapeutic El}3‘,(:l'llIS_. and by the
`;:Jlll(:'/I!}1F‘ll'({‘l‘li()|‘lS‘ by which they are prcsentetl. The hioavailahility
`and pmcnmd (_.ffic;u,-_y of an agent also are tletcrltitnetl by the
`[heI.flP,_.um_. targets. which are governetllliy-tltsease ctit>ltu;_v_
`[rm umnplt,-_ treatment ol a superficial nitcction oi the cor-
`mm while possibly wquil.i,1g sustained tlelivcry to enable less
`‘
`atlministration oi" antiniierohial therapy, does not in-
`frctplellt
`Wm,“ Smcigll (_g{;n¢;i(_lL:]‘:l[ilJI1.*i ot corneal |‘1<:‘l'l1I(.‘aEIt}II‘t)l' access to
`mu Lmflet I-i_i.;_c;|_[c, In this ei:-ctttttstaitce, protlttet tlcstgn Imgltt he
`dimcwd mwmd the rctluction ol any corneal or s_eleral trans-
`port
`in that these would he rc}.‘,artletl_ as tlrug lost trom‘the tar-
`tiet site. ()1: the other lomtl, a recalcitrant ease oi uvcitis ma_v
`require hotli topical and systctttie atlministr:tti_on of anti—_inilam-
`matory zujgents so as to clumnate the coiidtttoit.
`in this case,
`}m“.m,,v.,-‘ ”—;..1g-port to the nvea, an nttt.-rnal tissue, is tl(.‘.‘iiF£|l)l{.'.
`(;|mmio diseases associated with =l,L".iIl.é., like glaucoma. may
`,,m,_.,m[,[e to routine atlmittistration of a topical medica-
`1),".
`tion 1-Iw m,-gm‘ ]1owcve1', may he tleterminctl by the particular
`n‘|[-_:(_-[]3]‘|i:-;]]] for treating‘, the disease. For instance. a tlrug influ-
`cuming the ,t_i,t:ticratio|1 of aqueous humor may target the iris
`
`OP!-lTH.€>.LFv1IC PFIEPAFIATJONS
`
`911
`
`ciliary hotly, whereas a drug int'lue-neing the outtlow of aqueous
`humor might target the trahccular nteshwork that opens into
`the canal ol'St.'ltlet11In. The inherent characteristics of the drug
`also will determine, in part. any need for sustained delivery. lr:
`,l2L‘1Ie‘rtll, a lipophilie agent will he ahsorhetl readily into the lipo-
`pltilie corneal epitlteliuni, whereas an ionic or h_vtlropliilic agent
`will he :l.l‘lSUl‘ll{)(l more slowly. lint corneal permeation may still
`he a significant barrier to tleliyery at the target tissue even for
`a lipophilic drug, lteealuse transport tltrough the largely aque-
`ous stroma is still 1'eqniretl, ’l‘|1e capacity of the epitlieliunl for
`the tlrug, in part eontrolletl by its ptlrtititiiiilig cllaracteristics,
`rna}-' govern any n