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Running Head: DRUG DELIVERY SYSTEM 1

DEVELOPMENT AND CHARACTERIZATION OF A CONTROLLED-RELEASE

CIPROFLOXACIN HYDROCHLORIDE DRUG DELIVERY SYSTEM

Samar Z. Al-sa!!a1

1Department of pharmaceutical Sciences, College of Pharmacy, Princess

NourahBintAbdulrahman University, Alriyadh, Saudia Arabia

Aiman A. "#aida$%&

Department of Pharmaceutical !echnology, "aculty of Pharmacy, #ordan University of Science

and !echnology, $rbid, #ordan,

Alsa'ed A. Sallam(&

%Speciali&ed Pharmaceutical 'esearch Company, Amman, #ordan

Mu$a) S. Salem*

+,rresnding Au$r/s 0ame

+2ne 0um#er

+Email Address

Keywords

,n$rlled drug deli3er' s's$em& ,ir4l5a6in H'dr6lride& 7an$an gum& ,ar#l 8(*2&

2r'lene gl'6l& Gel-4rming s's$ems.


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DRUG DELIVERY SYSTEM %

A!STRACT

Co"#e$#,ir4l5a6in H'dr6lride 9,7-H,l; is an an$i#i$i6 used $ $rea$ #a6$erial

in4e6$ins in man' di44eren$ ar$s 4 $e #d'. I$ des n$ !r< 4r 3iral in4e6$ins 94r e5amle&

$e 6mmn 6ld E44e6$i3eness 4 ,7-H,l and a$ien$ 6mlian6e 6uld #e enan6ed $rug

drug deli3er' s's$em en6uraging leng$' drug release and $ere4re imr3ing i$s usage

in$er3als.

O%&e'#()eT u$line de3elmen$ and 6ara6$eri)a$in 4 a 6n$rlled-release 6ir4l5a6in

'dr6lride drug deli3er' s's$em. Te aim 4 drug deli3er' s's$em is $ gi3e 6ir4l5a6in

'dr6lride 9,7-H,l; in 6n$rlled release !a'.

Me#*odsTe s$ud' as #een !r


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DRUG DELIVERY SYSTEM *

salad dressings& 4r e5amle; and a s$a#ili)er 9in 6sme$i6 rdu6$s& 4r e5amle& $ re3en$

ingredien$s 4rm seara$ing;.


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DRUG DELIVERY SYSTEM B

INTRODUCTION

,ir4l5a6in H'dr6lride 9,7-H,l; als


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DRUG DELIVERY SYSTEM F

$i6al and r s's$emi6 dsage 4rms1. 7an$an gum 97G; is a l'sa66aride


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DRUG DELIVERY SYSTEM

LITERATURE SURVEY

Man' resear6ers re3ie!ed 6ir4l5a6in 4rm #i-degrada#le 6msed 4 $ri-6al6ium

sa$e 9T.,.2;& 6al6ium sa$es 'dr5'aa$i$ie 9H.A.2; and $ri-6al6ium sa$e

9T.,.2;& 6ir4l5a6in 9,..7;& and (


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DRUG DELIVERY SYSTEM

imlan$s 4r #ne in4e6$ins/ l6al $rea$men$& as ma>ri$' 4 $e s's$ems 4 drug deli3er' release

an$i#i$i6 4r 3er' less $ime and e5$ended in$ra3enus an$i-mi6r#ial $rea$men$ 94r a$ leas$ 4ur

$ si5 !ee


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DRUG DELIVERY SYSTEM 8

MATERIALS AND METHOD

M/#er(/,s

,ir4l5a6in H'dr6lride 9,7-H,l; and ,ir4l5a6in =ase 9,7-#ase; !ere US2

grades and !ere gi4$ samles 4rm $e Ara# 2arma6eu$i6al Manu4a6$uring ,. L$d.& 9A2M;

9Alsal$& ?rdan;.7an$an Gum 97G;& ,ar#l-8(* 9,-8(*;& Eudragi$ RL 1& and E$'l

,ellulse !ere 4 arma6eu$i6al grade and !ere gi4$ samles 4rm $e Ara# 2arma6eu$i6al

Manu4a6$uring ,. L$d.& 9A2M; 9Alsal$& ?rdan;.Trie$'l ,i$ra$e US20& Di#u$'l 2$ala$e

US20& and 2l5amer * and !ere gi4$ samles 4rm $e Ara# 2arma6eu$i6al

Manu4a6$uring ,. L$d.& 9A2M; 9Alsal$& ?rdan;.H'dr6lri6 a6id 9H,l;& (K& reagen$ grade& n-

"6$'l al6l& reagen$ grade& A@uagen$ 6msi$e B& 4ree 4rm 'ridine& ne 6mnen$ re-agen$

4r 3lume$ri6 Jarl-is6er $i$ra$in& Sdium 6lride& e5$ra ure& 2Eur& US2& =2& 2$assium

=rmide& IR& Se6$rs6' grade& A6e$ni$rile& is6ra$i6 H2L, grade 9%B* nm;& A6e$i6 A6id

gla6ial& H2L, grade. All $e re3ius reagen$s !ere ur6ased 4rm Sarlau& Sain. 2r'lene

Gl'6l 92G;& Sdium a6e$a$e $ri'dra$& Me$anl& is6ra$i6 H2L, grade 9%B* nm;& Sarlau&

Sain. a$er 4r H2L,& A6rs. Tigl'6la$e medium #ase 9enri6ed; a66. T ,D, 4r

mi6r#ilg'& Mer6


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@.s. $ B ml $ rdu6e a slu$in 6n$aining 7G .B er6en$ !!: ,-8(* .B er6en$ !!:

,7-H,l .B er6en$ !! 9SD1;& r $ rdu6e an$er slu$in 6n$aining 7G .B er6en$ !!:

,-8(* .B er6en$ !!: ,7-H,l .Ber6en$ !!: 2G .B er6en$ !! 9SD%;.

Te slu$in !as sra' dried !i$ =U,HI 18 mini-sra' dr'er& S!i$)erland. i$ $e

4ll!ing 6ndi$ins: 2um# 9(-*mlmin;& Tem. 9Inle$ Tem. 1 N % ,& u$le$ Tem. F N

%degree 6en$igrade;& Asira$r 9*;& air 4l! 6n$rl 9BB;.

F/%r('/#(o" o. Powders .or Dr+7 De,()ery Sys#e9s /"d O'+,/r I"ser#s

Te sra' dried !der SD% !as mi5ed !i$ sui$a#le amun$s 4 $e 4ree drug ,7-H,l

$ rdu6e di44eren$ ra$is 4 drug $ ma$ri5 9sra' dried rdu6$; !ders and $ rdu6e

di44eren$ $a#le$ 4rmulas& as s!n in T/%,e :. SD% !ders !ere 6sen 4r 4a#ri6a$in 4 $e

drug deli3er' s's$ems and n$ SD. Ta$ is #e6ause SD1 !ders s!ed signi4i6an$ redu6$in in

drug 6n$en$ #' gamma s$erili)a$in !ile SD% didn/$. Te nminal ,7-H,l dse in $e

medi6a$ed inser$s !as 6sen $ #e F.%B mg. ,mnen$s 4 !der 4 ea6 4rmula !ere mi5ed

$rugl' in small 3ials !i$ a sa$ula 4r % minu$es #e4re 6mressin& $en 6mressing $e

!der mi5$ures !i$ $e el 4 'drauli6 ress in 4la$-4a6ed $a#le$s 4 B millime$er diame$er&

#' ali6a$in 4 $usand Jg 4r6e 4r B se6nds.

Ta#le$s !ere $en 4ilm 6a$ed !i$ Eudragi$ RL 1 9RL; l'mer slu$in 9RL 1K

dissl3ed in is-rranll FK: a6e$ne *K sl3en$ s's$em& di#u$'l $ala$e 1K !! 4

RL !eig$& and $rie$'l 6i$ra$e %K !! 4 RL !eig$; #' diing $e $a#le$s in $e l'mer

slu$in $en rem3ing and la6ing i$ n $e Te4ln la'er and le$ i$ dr' 4r .B ur a$ *,.

Diing again in l'mer slu$in and la6ing i$ n Te4ln sur4a6e n $e $er $a#le$ 4a6e& and

le$ i$ dr' 4r .B ur a$ * ,. Ta#le$s/ $i6


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In $is s$ud'& $e $e6ni@ues $a$ u$ili)ed in 6ara6$eri)a$in 4 $e riginal drug alne as

!ell as $e reared sra' dried !ders& !ere 7-ra' di44ra6$me$r' 97RD; using 7-Ra'

Di44ra6$me$er: 2 1%8& 2ilis& Hland& s6anning ele6$rn mi6rs6e 9SEM;EI 92ilis;&

Ouan$a %& Hland& di44eren$ial s6anning 6alrime$r' 9D.S.,; Simad)u Di44eren$ial S6anning

,alrime$er D.S.,-B 6nne6$ed !i$ I=M ersnal s's$em& ?aan& $erm gra3ime$ri6 anal'sis

9TGA; Simad)u Term gra3ime$ri6 Anal')er TGA-B 6nne6$ed !i$ I=M ersnal s's$em&

?aan& and 4urier $rans4rm in4rared se6$rs6' 9TIR;Ma$$sn In4ini$' GldTMTIR

Se6$rs6'& ,de 0. RD(1R0I& USA. A3erage re radius& $$al re 3lume& e5$ernal

sur4a6e area and se6i4i6 sur4a6e area 4 $e sra' dried s's$em !ders SD1 and SD% !ere

iden$i4ied u$ili)ing $e Mul$iS$a$in Hig Seed Gas Sr$in Anal')er: 0"VA %% 3. F.11&

Ouan$a6rme ,.& USA. Te $rue densi$' 4 $e sra' dried s's$em !ders !as de$ermined

using Helium 2'6nme$er: Ul$ra'6nme$er 1 3. %.%& Oua$a6rme ,.& USA.

Mi6r#ilgi6al Sus6e$i#ili$' Tes$ S$udies

Te release 4 ,7-H,l 4rm $e drug deli3er' s's$ems !as in3es$iga$ed #a6$erilgi6all'

as seen in igure 1 in agar la$es seeded !i$ Staphylococcus aureus%B8%B 9S( aureus;& and

Pseudomonas aeruginosa%B( 9P( aeruginosa; as $e $es$ mi6rrganisms.

Using Mueller Hin$n Agarla$es. S$erili)e $e 6u #' immersing i$ in e$anl $en 4laming&

and la6ing i$ n $e la$e& $en u$$ing $e samle r s$andard in $e 6u& ei$er in susensin

4rms 4 sra' dried !der in dis$illed !a$er r as !der. ,3er $e e$ri dis. 2u$ in

in6u#a$r 9( N .B

,; 4r %* urs r mre. Ini#i$in )nes/ diame$ers !ere assessed arund

$e 4rmula$ins. S$udies !ere 6arried u$ in $rili6a$es.

S#er(,(;/#(o"


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DRUG DELIVERY SYSTEM 1%

Sra' dried !ders 9S.D1 and S.D%; and 4ilm 6a$ed 6ular inser$s 94 1 4rmula; !ere

s$erili)ed !i$ $e el 4 gamma radia$in. Te sra' dried !ders !ere gi3en an 3erall dse

4 1 M Rad 9mega rads;& % M rad& and ( M rad. Tese $ree samles 4 $e !der& ea6 ne

!ere e5sed $ di44eren$ dses 4 gamma radia$in& ea6 samle 4 $ree runs. Te 1 4ilm

6a$ed 6ular inser$s !ere gi3en a $$al amun$ 4 1 M Rad. Tis !as dne a$ $e ?rdan A$mi6

Energ' ,mmissin& Amman& ?rdan. Sra' dried ma$ri5 s's$ems !ere assessed 4r 6n$en$

e5amine& in 3i$r release r4ile& and 4r 6lr. S$erili)ed 6ular inser$s !ere e3en assessed 4r

in$a6$ness and 6lr 4 6ular inser$s& as !ell as 4r $eir in 3i$r release r4ile $ 6e6< gamma

radia$in/s in4luen6e n $ese 6ara6$eris$i6s. A s$erili$' $es$ n s$erili)ed 6ular inser$s !as

6arried u$ as men$ined #' US2 using $igl'6la$e susensin. Te $es$ !as 4 4a#ri6a$ed

6ular inser$s and !as dne $ 6e6< !e$er $e' !ere s$erile r n$ a4$er $e' !ere s$erili)ed

!i$ gamma radia$in.

S#/%(,(#y S#+d(es

S$a#ili$' resear6es !ere er4rmed n sra' dried !ders 9SD1 and SD%;. Su44i6ien$

amun$s 4 sra' dried !ders 9e6$ed $ e5aggera$ed

6ndi$ins 4 $emera$ure& umidi$'& and lig$ 4r a66elera$ed s$a#ili$' s$ud'. 9( ,& * ,& B

,& F ,& *,PBKRH& and $ s$a#ili$' in Am#er #$$les and in ,lrless e$ri dises;

Samles !ere !i$-dra!n a$ di44eren$ $ime #rea


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DRUG DELIVERY SYSTEM 1(

remaining drug 3ersus $ime in da's& !ere $e sle is e@ual $ -J%.(( and J is C$e

degrada$in ra$e 6ns$an$.

Dr+7 Co"#e"# (" S6r/y Dr(ed Prod+'#s1 mg !der !as sa


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DRUG DELIVERY SYSTEM 1*

ml samle a$ di44eren$ $ime in$er3als u $ %F urs and rela6ing i$ !i$ B millime$er 4

disslu$in media. Te samles !ere anal')ed using $e re3ius H2L, me$d 4 anal'sis.

I" V(#ro Re,e/se o. C.$-H', Fro9 O'+,/r I"ser#s

Te inser$s !ere la6ed in$ ened disslu$in #as


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DRUG DELIVERY SYSTEM 1B

RESULTS

P*ys('/, Pro6er#(es

TIR F(7+re < re3ealed $e 6n3ersin 4 4ree ,7-H,l in$ 6mle5ed ,7-H,l. In $e

sra' dried rdu6$s 4 7G: ,7-H,l $ere is a ne! ea< !i6 6uld #e a s$rng e3iden6e 4

in$era6$in #e$!een 7G and ,7-H,l. Tis in$era6$in is due $ 6ela$in #e$!een $e ," 4

$e *-5-@uinline mie$' and ,""H 4 $e ,7-H,l !i$ $e ,aPPand .1K MgPP4 $e

'drili6 l'mer 7G. Tese sr$ 4 ini6 in$era6$ins a3e #een rer$ed re3iusl' in

li$era$ure1*-1B. ,ar#l-8(* as 6ar#5'li6 a6id 4un6$inal grus $a$ !ere used $ de6rease $e

in$era6$in #e$!een ,7-H,l and 7G and $us ,-8(* els in enan6ing $e release.

Te 7RD a$$ern s!n in F(7+re 3 4 $e 6r's$al 4rm 4 ,7-H,l is 6ara6$eris$i6 4 $e

6r's$al 4rm !i$ dis$in6$l' di44eren$ ea< si$ins1F. ile& $e 7RD a$$erns 4 ,7-H,l SD

and 4 SD1 and SD% sra' dried ma$ri5 s's$ems e5i#i$ n de4ini$e di44ra6$in ea


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DRUG DELIVERY SYSTEM 1F

sur4a6es and are mu6 mre regular in sae $an $e SD1 granules. Tis indi6a$es $a$ $e

66urren6e 4 2.G did 6nsidera#l' a44e6$ $e mrlgi6al 4ea$ures 4 $e sra' dried ar$i6les

as !ell as $eir si)e. Un si)e anal'sis 4 ar$i6le& SEM anal'sis s!ed a gd rerdu6i#ili$'

and mgenei$' 4 sae and si)e amng $e seara$e #a$6es 4 samles. r ar$i6le si)e

anal'sis 4 SD1 *.BK $ .BK 4 $e ar$i6les are F m& !ile 4 SD% K $ 8K 4 $e

ar$i6les are F m.

Te resul$s 4 $rue densi$' measuremen$ !ere $e a3erage 4 $en runs 4r ea6 sra' dried

!der. Te resul$s s!ed $a$ $e SD% densi$' 91.BFF( N .1%1 g6m(;& !as iger $an SD1

densi$' 91.*B* N .F g6m(;. Tis 6uld #e due $ $e resen6e 4 2G in SD% and n$ in

SD1.Te resul$s 4 sur4a6e area measuremen$ are gi3en in T/%,e


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,n$rlled release is s!n #' a l$ 4 K release 3s. $ime and n$ 4rm ini#i$in )ne.

Ini#i$in )nes rdu6ed #' SD% 4rmulae a3e grea$er diame$ers $an $se rdu6ed #' SD1

4rmulae. Tis 6an #e a$$ri#u$ed $ 2G rle in SD% 4rmulae $is e44e6$ is due $ di44usin ra$er

$an s'nergis$i6 e44e6$ rdu6ed #' 2G.

S#er(,(;/#(o" o. #*e S6r/y Dr(ed Sys#e9s

Te sra' dried 9SD; s's$ems SD1 and SD% a3e #een a44e6$ed #' $e s$erili)a$in !i$

gamma radia$in as s!n in T/%,e 3. SD1 !ders s!ed signi4i6an$ redu6$in in drug

6n$en$ #' gamma s$erili)a$in. ile in $e 6ase 4 SD%& 4rmulas !ere a44e6$ed #' % and ( M

Rad. ra$er $an 1 M Rad. Tis 6an #e e5lained mainl'& $a$ $e l'mer is a44e6$ed #'

s$erili)a$in& and 2G is a s$a#ili)ing agen$ in SD% 4rmula$ins. Tis e44e6$ als !as 3eri4ied #'

$e de6reased disslu$in #ea3ir as s!n in F(7+res > /"d ?. Te 6lr 4 $e sra' dried

s's$ems did n$ 6ange signi4i6an$l' due $ s$erili)a$in !i$ gamma radia$in. =ased n $ese

4indings& SD% s's$em !as 6sen $ #e used in $e 4inal 6ular inser$ reara$ins ra$er $an

SD1 s's$em.

S#er(,(;/#(o" o. #*e F(,9 Co/#ed O'+,/r I"ser#

Te 4ilm 6a$ed 6ular inser$s 4 1 !ere s$ill in$a6$ and $eir 6lr did n$ 6ange un

s$erili)a$in !i$ 1 M Rad gamma radia$in. Teir disslu$in #ea3ir !as 3er' similar $ $a$

!i$u$ s$erili)a$in as s!n in F(7+re @. Tese inser$s !ere n$ a44e6$ed #' s$erili)a$in.

S#er(,(#y Tes#s

Te s$erili$' $es$ !as assed #' all $e s$erili)ed 1 4ilm 6a$ed 6ular inser$s. Te' !ere

4und s$erile a$ $e $ree di44eren$ in6u#a$in $emera$ures %B& (& and *% , a4$er ( da's. Te

6n$en$s 4 all $e $es$ $u#es !ere 4und 6lear 3isuall'& !i$u$ an' de3elmen$ 4 $ur#idi$'

andr sur4a6e gr!$. Te 6ular inser$s $es$ed me$ $e US2 re@uiremen$s 4 $e $es$ 4r s$erili$'.


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19/31


mre #3ius a$ iger $emera$ures. SEM $mi6rgras 4 SD1 and SD% ma$ri5 s's$ems

s$red under ( , and * , a4$er $ree mn$s s!ed $a$ $e mi6r6asules 4r #$ SD1 and

SD% !ere 6llased and srin


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Te resul$s 4 in$rinsi6 disslu$in $es$ing 4 ,7-H,l drug 4rm $e sra' dried s's$ems

SD1 and SD% 6mared $ $e drug dis< alne in .8 K 0a,l are summari)ed in F(7+re ::.

Sme @uali$a$i3e 6n6lusins are 91; release 4 ,7-H,l 4rm drug !der dis


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DRUG DELIVERY SYSTEM %1

assa' 9%; Te $imes 4r B er6en$ 9$BK; and er6en$ 9$K; 4 drug release and mean

disslu$in $ime 9M.D.T; !ere r3ided as mean 3alues 4 $ree readings.

Te release 4 drug 4rm 'drili6 l'mers aened largel' during $e l'mers/

disslu$in::. Un6a$ed SD% inser$s erded 6mle$el' a4$er $e release 4 $e laded drug&

!e3er& $e mean disslu$in $ime& MT& !as 1% ur 4r 1 un6a$ed inser$. Te MT !as mu6

sr$er 4r !ere i$ !as * min 4r $e un6a$ed inser$. As $e er6en$age 4 SD% in $e drug

deli3er' s's$em in6reased&)!in6reased in a nn-linear 4asin*%-**. Te ra$is 4 $e 4ree drug

and SD% a$ e5$remi$ies grea$l' a44e6$)!!ile& $e in$ermedia$e ra$is a3e a l!er e44e6$ n

)!. Te sl! ra$e 4 disslu$in 4 7G resul$s in a larger $ime 4r 6mle$in 4 $e drug

release. Te ra$e 6ns$an$ *$a$ des6ri#es $e sle 4 release 4 drug is #ased n $e l'mer&

ma$ri5 $i6


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DRUG DELIVERY SYSTEM %%

regressin anal'sis%1-%. i$$ing $e release da$a $ Higu6i mdel ga3e $e larges$ R-s@uared

3alues 4r $ese un6a$ed inser$s reara$ins. Te R-s@uared 3alues s$rngl' indi6a$ed $a$ $e

release me6anism is mainl' 6n$rlled #' i6


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DRUG DELIVERY SYSTEM %(

DISCUSSION

Sra' dried !ders !ere reared #' 6uling a mdel drug 6ir4l5a6in 'dr6lride

9,7-H,l; !i$ 5an$an gum 9 7G ;& 6ar#al 8(* 2 9 ,-8(* ; in $e resen6e r a#sen6e 4

r'lene gl'6l 92G;. Te in$era6$in 4 ,7-H,l !i$ 7G and ,-8(* !as 6lari4ied #' TIR

and DS,. Ini6 in$era6$in #e$!een ,7-H,l and 7G and ,-8(* seemed $ #e $e main

in$era6$in $a$ de$ermined $e 'si6al 6ma$i#ili$' and releasing rer$ies. Te

rerdu6i#ili$' 4 sra' dr'ing $e6ni@ue !as mani4es$ed #' $e assa' 4 drug 6n$en$ and

in$rinsi6 disslu$in #ea3ir 4 $e sra' dried !ders as !ell as $er 'si66emi6al

6ara6$eri)ing $e6ni@ues su6 as DS,& TIR& 7-ra'& SEM. SD% sra' dried !ders $a$ !ere

6n$aining 7G& ,-8(*& 2G and ,7-H,l !ere mre s$a#le $an SD1 !ders $a$ !ere

6n$aining 7G& ,-8(* and ,7-H,l.2'si66emi6al 6ara6$eri)a$in 4 $e sra' dried ma$ri5 s's$ems s!ed $e amrus

6ara6$er in $e sra' dried ma$ri5 s's$ems& !i6 !as due $ 6mle5a$in #e$!een $e drug

and $e l'mers as !ell as due $ sra' dr'ing $e6ni@ue i$-sel4. Te ar$i6les !ere

6ara6$eri)ed as mi6r6asules ra$er $an a slid ma$ri5 a3ing si)e #el! F m& sm$

sur4a6e and seri6al sae. Te mi6r6asules !ere 6llased and srin


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DRUG DELIVERY SYSTEM %*

* 4rmula 9a3ing 4ree ,7-H,l ( milligram: S.D% 1( milligram; disla's an ali


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DRUG DELIVERY SYSTEM %F

ACKNOBLEDGEMENTS

e !uld li


27/31


REFERENCES

1. Al-Jassas RS& El-Ja$i# MM. "$almi6 6n$rlled release in si$u gelling s's$ems 4r

6ir4l5a6in #ased n l'meri6 6arriers. DrudDeli3& %8 Ar 1F9(;: 1*B-B%.%. Al-Rema!i MMA. %(. rmula$in 4 a uni3ersal 6n$rlled release 'drili6 l'mer

mi5$ures read' 4r dire6$ 6mressin. 2H. D. Tesis& ?rdan Uni3ersi$' 4 S6ien6e and

Te6nlg'& Ir#id& ?rdan.& 9. 1*(-1*B&%%-%1*;.

(. =ara$ S& Hirema$ SR. "6ular deli3er' s's$ems 4 e4l5a6inmes'la$e. 2arma)ie 1888

B*91;: BB-B.

*. ,ar 0A& Jli J& Ali A& An!er A. "$almi6 deli3er' 4 6ir4l5a6in 'dr6lride

4rm di44eren$ l'mer 4rmula$ins: in 3i$r and in 3i3 s$udies. D De3 Ind 2arm& %( %8

9%;: %1B-%%1.

B. ,ar 0A& Jli J& Ali A. 2reara$in 4 in si$u-4rming $almi6 gels 4 6ir4l5a6in

'dr6lride 4r $e $rea$men$ 4 #a6$erial 6n>un6$i3i$is: in 3i$r and in 3i3 s$udies. ?

2arm S6i& %( 8% 9%;: *-*1(.

F. ,ilin ?=& Hare TR& I!a$a 0G& =elau I& Dlman ,H& Langer R& Jane DS. A drug-

elu$ing 6n$a6$ lens. In3es$ "$alml Vis S6i& %8 ?ul B9;: ((*F-B%.

. ,s$a 2& L# MS. Mdeling and 6marisn 4 disslu$in r4iles. E ? 2arm S6i %1 1(:

1%(-1((.. Dilna!a)& .& W Sa& S. J. 9%1*;. 0an$e6nlg'-=ased "$almi6 Drug Deli3er'

S's$em. In 6al ,n$rlled Drug Deli3er' 9. %%B-%*1;. Sringer US.8. D@ ,. Te me6anisms 4 drug release 4rm slid disersins in !a$er-slu#le l'mers. In$

? 2arm& %% %(19%;& 1(1-**.

1. lren6e AT& A$$!d D.%F. 2'si66emi6al 2rin6iles 4 2arma6'. *$ Ed. Lndn:

2arma6eu$i6al 2ress.11. Ga3ini E& ,e$ni 2& ,ssu M& Al3are) MG& Sae$$ne M& Giun6edi 2. 2LGA mi6rseres

4r $e 6ular deli3er' 4 a e$ide drug& 3an6m'6in using emulsi4i6a$insra'-dr'ing as

$e reara$in me$d: in 3i$r in 3i3 s$udies. E ? 2arm =i& %* Mar B9%;: %-1%.


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DRUG DELIVERY SYSTEM %8

%*. 2arma 2l'mers& Eudragi$& =asi6 In4 %& 2arma 2l'mers& Rm& D-F*%B Darmas$ad$&

German'.

%B. Re)3ani& Z.& W Sa#aei& M. 9%1*;. =inan6msi$es #ased n algina$e and

6i$sanla'ered du#le 'dr5ide !i$ 6ir4l5a6in drug: In3es$iga$in 4 s$ru6$ure and

6n$rlled release rer$ies. 2l'mer ,msi$es. D"I: 1.1%6.%(8

%F. Rina


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DRUG DELIVERY SYSTEM (

(*. S$>6i6& ?.& D>uri6& Z.& W ,rrigan& ". I. 9%1*;. A ,ase S$ud' 4 In Sili6

Mdelling 4 ,ir4l5a6in H'dr6lrideMe$alli6 ,mund In$era6$ins. AA2S

2armS6iTe6& 1B9%;& %-%.

(B. T#ias& I. S.& Lee& H.& Engelma'r ?r& G. ,.& Ma6a'a& D.& =e$$inger& ,. ?.& W ,ima& M. ?.

9%1;. Zer-rder 6n$rlled release 4 6ir4l5a6in-H,l 4rm a reser3ir-#ased&

#iresr#a#le and elas$meri6 de3i6e. ?urnal 4 ,n$rlled Release& 1*F9(;& (BF-(F%.(F. 2a!ar& A. Y. 9%1%;. rmula$in and e3alua$in 4 n3el #idegrada#le imlan$a#le drug

deli3er' s's$ems 4 6ir4l5a6in 'dr6lride.(. 2a!ar& S. D.& Gada3e& M. V.& ?ada3& S. L.& W Gai

ARTI,LE DESIG0 A0D EVALUATI"0 " 2"LYMERI, ",ULAR DRUG DELIVERY

SYSTEM "R ,"0TR"LLED DELIVERY " ,I2R"L"7A,I0 HYDR",HL"RIDE.

(. 0gu'en& D.& Hui& A.& ee


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