FORMULATION AND EVALUATION OF PECTIN/HPMC BASED

MATRIX TABLETS OF ZIDOVUDINE

M. Pharm. Dissertation Protocol Submitted to

Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore 5600!
By
MR.CHAVAN SAMADHAN SHIVAJI
B.Pharm

Under the G"idance
of

Dr. M. S. SRINATH
M.pharm, Ph.D
Deparme! "# Pharma$e%&$'
S.E.T(' COLLE)E OF PHARMAC*
S# R# $agar, %har&ad5'000(
+,-+.+,-/
0


RAJIV )ANDHI UNIVERSIT* OF HEALTH SCIENCES,
BAN)ALORE, 0ARNATA0A
ANNEXURE.II
PROFORMA FOR RE)ISTRATION OF SUBJECTS FOR
DISSERTATION
-. NAME OF THE CANDIDATE
AND ADDRESS
)r#*H+,+$ S+)+%H+$ SH-,+.-
%/01# 23 0H+R)+*/U1-*S
S/14s *255/G/ 23 0H+R)+*6,
S#R#$+G+R,
%H+R7+%85'000(
+. NAME OF THE INSTITUTION S/14s *255/G/ 23 0H+R)+*6,
S# R# $+G+R,
%H+R7+%85'000(
/. COURSE OF STUD* AND
SUBJECT
)+S1/R 23 0H+R)+*6 -$ 0H+R)+*/U1-*S
1. DATE OF ADMISSION TO
COURSE
(59069(0!(
2. TITLE OF THE TOPIC
FORMULATION AND EVALUATION OF PECTIN/HPMC BASED MATRIX
TABLETS OF ZIDOVUDINE
!
3. BRIEF RESUME OF THE INTENDED 4OR0
3.- NEED FOR THE STUD*5
2ral ro"te is the :ost ;referred ro"te for ad:inistration of dr"gs# 1a<lets are the
:ost ;o;"lar oral for:"lations availa<le in the :arket and ;referred <y the ;atients and
;hysicians alike# -n long8ter: thera;y for the treat:ent of chronic disease conditions,
conventional for:"lations are re="ired to <e ad:inistered in :"lti;le doses, and therefore
have several disadvantages
!
#
*ontrolled release >*R? ta<let for:"lations are :"ch desira<le and ;referred
for s"ch thera;y <eca"se they offer <etter ;atient co:;liance, :aintain "nifor: dr"g levels,
red"ce dose and side effects, and increase safety :argin for high;otency dr"gs#
(
+ccording to one of the recent re;orts of 7H2 +c="ired -::"nodeficiency Syndro:e
>+-%S? e;ide:ic sho&ed @'#0 :illion ad"lts and (#@ :illion children &ere living &ith
h":an i::"nodeficiency vir"s >H-,?# 1he ann"al n":<er of +-%S deaths can <e eA;ected
to increase for :any years to co:e, "nless :ore effective and ;atient co:;liant anti8
retroviral :edications are availa<le at afforda<le ;rices# 1he :ajor dra&<acks of
antiretroviral dr"gs for the treat:ent of +-%S are their adverse side effects d"ring long8ter:
thera;y, ;oor ;atient co:;liance and h"ge cost of the thera;y#
,@,

Bidov"dine, the first anti H-, dr"g a;;roved for clinical "se and is &idely
"sed for treat:ent of +-%S either alone or in co:<ination &ith other antiviral agents#
Ho&ever, the :ain li:itation to thera;e"tic effectiveness of Cidovidine is its dose8de;endent
he:atological toAicity, short <iological half8life, and ;oor <ioavaila<ility#
5
1reat:ent of +-%S "sing conventional for:"lations of Cidovidin is fo"nd
to have :any dra&<acks s"ch as adverse side effects d"e to acc":"lation of dr"g in :"lti8
dose thera;y, ;oor ;atient co:;liance
6
and high cost# So, s"stained release for:"lations can
overco:e so:e of these ;ro<le:s associated &ith the conventional for:"lations# 1he dr"g
is freely sol"<le at any ;H, hence j"dicio"s selection of release retarding eAci;ients is
necessary for achieving constant in vivo release# 1he :ost co::only "sed :ethod of
:od"lating the dr"g release is to incl"de it in a :atriA syste:#
D
)atriA <ased controlled and
s"stained release ta<let for:"lations are the :ost ;o;"lar and easy to for:"late on a
co::ercial scale in an ind"stry# 1he :atriA ta<lets can <e ;re;ared via &et gran"lation or
<y direct co:;ression :ethod# )any ;oly:ers have <een "sed in the for:"lation of :atriA
<ased *ontroled and s"stained release delivery syste:s#
(
Hydro;hilic ;oly:ers like hydroAyl ;ro;yl :ethylcell"lose
H0)*?,:ethylcell"lose, sodi": car<oAy :ethylcell"lose, car<o;ols

and ;olyvinyl alcohol
'
are <eing "sed for the ;re;aration of *ontrolled release for:"lations of different dr"gs#
Hydro;hilic ;oly:er :atriA syste:s are &idely "sed for designing oral controlled dr"g
delivery dosage for:s <eca"se of their fleAi<ility to ;rovide a desira<le dr"g release ;rofile,
cost effectiveness, and <road reg"latory acce;tance#
E

0ectin, a nat"ral ;oly:er is a str"ct"ral co:;onent of ;lant cell &all# 1he non8
toAicity and lo& ;rod"ction costs :ake the: of great interest for the for:"lation of
s"stained release as it ra;idly for:s visco"s sol"tion and gels on contact &ith a="eo"s
:edia
!0

$o&adays a ne& foc"s has <een directed to&ards investigating the "se of
;oly:er <lends of ;har:ace"tically a;;roved ;oly:eric :aterials as :atriA eAci;ients to
retard dr"g release
D
# 1he :ost convenient &ay to achieve s"stained release of active agent
involves ;hysical <lending of dr"g &ith ;oly:er :atriA, follo&ed <y direct co:;ression,
co:;ression :olding, injection :olding, eAtr"sion, or solvent casting &hich res"lts either in
:onolithic device or in s&ella<le hydrogel :atriA#
!!,!(,!@
1herefore this st"dy is ai:ed to investigate the effect of vario"s <lends of
;ectin 9H0)* on the release of Cidov"dine fro: the :atriA ta<lets and o<tain a controlled
release of dr"g#
3.+ REVIE4 OF LITERATURE5
5iterat"re revie& for "ndertaking the st"dy &as carried o"t <y referringF
,ario"s standard <ooks#
Standard national and international jo"rnals#
-nternet <ro&sing#
%irectly co:;ressed theo;hylline ta<lets, containing co::ercial Aanthan >G?
>KeltrolH? Band a highly hydro;hilic galacto:annan >G? fro: the seeds of Mimosa
scabrella >a <raCilian leg":ino"s tree called <racatinga? as release8controlling agents, &ere
o<tained# G":s &ere "sed at , ', !(#5 and (5I >&9&?, either alone or in :iAt"re >GFG
!F!?# %"ring galacto:annan eAtraction ;rocess, the <io;oly:er &as dried in a scale ";, <y
vac"": oven >,2? or s;ray dryer >S%?# 1he in vitro dr"g release &as eval"ated at different
ti:e intervals d"ring ' h "sing a;;arat"s ! >US0 (6? at !00 r;:# 1he ;H of the dissol"tion
:edi": >!#? &as changed to #0 and 6#' after ( and @ h, res;ectively# 1a<lets containing
@
G>S%? res"lted in :ore "nifor: dr"g release than G>,2? ones, d"e to their s:aller ;article
siCe# 1he dr"g release decreased &ith the increase of ;oly:er concentration and all
for:"lations at (5I &9& of g":s sho&ed eAcessive s"stained release effect# 1he :atrices
:ade &ith alone G sho&ed higher dr"g retention for all concentrations, co:;ared &ith G
:atrices that released the dr"g too fast# 1he GG :atrices &ere a<le to;rod"ce near Cero8
order dr"g release
!
#
1he st"dy &as carried o"t to investigate s&elling and erosion <ehaviors of
hydro;hilic :atriA ta<lets "sing ;ectin and their i:;act on dr"g release# 1he :atriA ta<lets
&ere ;re;ared <y direct co:;ression "sing different ty;es of ;ectin# S&elling and erosion
st"dies of ;ectin :atriA ta<lets &ere carried o"t in vario"s :edia# 1he ;ectin :atriA ta<lets
for:ed a contin"o"s gel layer &hile in contact &ith the a="eo"s :edi": "ndergoing a
co:<ination of s&elling and erosion# 1he s&elling action of ;ectin :atrices &as controlled
<y the rate of its hydration in the :edi":# Release st"dies sho&ed that the s&elling and
erosion of :atrices infl"enced the dr"g release# 1he eAtent of :atriA s&elling, erosion and
diff"sion of dr"g deter:ined the kinetics as &ell as :echanis: of dr"g release fro: ;ectin8
<ased :atriA ta<lets
!5
#
+n atte:;t &as :ade to develo; once daily s"stained release :atriA ta<lets
of Stav"dine "sing ;"tative hydro;hilic :atriA :aterials s"ch as hydroAyl ;ro;yl :ethyl
cell"lose >H0)*? K) and *ar<o;ol ED0# 3or:"lation &ith a ;artic"lar concentration of
H0)* K) and *ar<o;ol ED0 eAhi<ited an eAtended dr"g release till the end of ( ho"rs
and sho&ed higher r val"es for Cero order ;lot, indicating that dr"g release follo&ed Cero
order kinetics# 1his finding reveals that they are ca;a<le of ;roviding al:ost Cero order dr"g
release
!6
#
1he floating :iA :atriA ta<lets of stav"dine &ere ;re;ared <y :elt
gran"lation :ethod# Bees&aA &as "sed as hydro;ho<ic :"ta<le :aterial# HydroAy;ro;yl
:ethylcell"lose >H0)*?, sodi": <icar<onate, and ethyl cell"lose &ere "sed as :atriAing
agent, gas generating agent, and floating enhancer, res;ectively# 1he floating lag ti:e of all
the for:"lations &as &ithin the ;rescri<ed li:it# +ll the for:"lations sho&ed good :atriA
integrity and retarded the release of dr"g for !( ho"rs
!D
#

3./ OBJECTIVE OF STUD*5
1he o<jective of the ;ro;osed st"dy areF8
!? 0re;aration of standard cali<ration c"rve of Bidov"dine#

6.
(? 0re;aration of ;ectin9 <ased :atriA ta<lets#
@? /val"ation of follo&ing ;ara:eters#
7eight variation of the ta<lets#
1hickness variation of the ta<lets#
Hardness deter:ination of the ta<lets#
S&elling and erosion st"dies#
/val"ation of ;ectin9H0)* <ased :atriA ta<lets for dr"g content and
in vitro release st"dies#
MATERIALS AND METHODS 5
MATERIALS 5
%r"gF Bidov"dine
$at"ral ;oly:erF 0ectin and H0)*
1a<let additives like l"<ricants and dil"ents#
6.- SOURCE OF DATA 5
-t &ill <e o<tained fro: the ;re;ared :atriA ta<lets <ased on la<oratory eA;eri:ents
and eval"ation#
6.+ METHOD OF COLLECTION OF DATA 5
A7 C"mpa&8&9&: '%;:5 *o:;ati<ility of dr"g &ith ;oly:ers &ill <e investigated
"sing 318-R s;ectrosco;y and differential scanning calori:etry >%S*?#
B7 Prepara&"! "# 'a!;ar; $a9&8ra&"! $%r<e "# =&;"<%;&!e
C7 Prepara&"! "# mar&> a89e'5 )atriA ta<lets &ill <e ;re;ared <y s"ita<le :ethod#
%ifferent <lends of ;ectin and H0)* &ill <e ;re;ared and then all ingredients &ill
<e ;assed thro"gh a 608:esh sieve# +ll the ingredients &ill <e :iAed thoro"ghly for
!5 :in"tes &itho"t additives and for a f"rther 5 :in"tes after addition of additives#
D7 Pre $"mpre''&"! '%;&e'5 1he ;re;ared <lends &ill <e eval"ated for <"lk density,
ta;;ed density, *arr4s indeA, angle of re;ose and Ha"sner4s ratio#
E7 P"' $"mpre''&"! '%;&e'5 1he ta<lets &ill <e eval"ated for dia:eter, thickness,
hardness, fria<ility and &eight variation#
5
F7 S?e99&!@ a!; er"'&"! '%;&e'.
)7 E'&ma&"! "# ;r%@ $"!e! 8: %'&!@ UV.'pe$r"'$"p&$ meh";#
H7 In vitro re9ea'e '%;:5 1he release st"dies &ill <e carried o"t "sing US0 JJKLL
dissol"tion a;;arat"s at the s;eed of 50 r;: "sing E00 :l of acid <"ffer >;H !#(?
for the initial ( ho"rs, follo&ed <y ;hos;hate <"ffer >;H 6#'? "ntil co:;letion of
dissol"tion# 1he dissol"tion :edi": is :aintained at @DM
o
*, at s;ecific intervals
sa:;le &ill <e &ithdra&n and eAa:ined for dr"g content "sing U,
s;ectro;hoto:eter#
6./ DOES THE STUD* REAUIRE AN* INVESTI)ATION OR INVENTION TO BE
CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALSB IF SO
PLEASE MENTION BRIEFL*.
$o#
6.1 HAS ETHICAL CLEARANCE BEEN OBTAINED FROM *OUR
INSTITUTION IN CASE OF 6./B
N" app9&$a89e.
6
C

REFERENCES5
!# *hien 6 7F $ovel %r"g %elivery Syste:s,editor# *hien 6# 7N )arcel %ekker, -nc#
$e& 6ork, U#S#+N !EE(# ;# !@E8E6#
(# ,yas S0, Khar R KF*ontrolled %r"g %eliveryF *once;ts and +dvances# editor# ,yas
S# 0#, Khar R K ,alla<h 0rakashan, %elhiN(00(# ;# !558E5#
@# Rich:an %, 3ischl )), Grieco )H, Gottlie< )S, ,ol<erding 0+, 5askin 25, et al.
1he toAicity of aCidothy:idine >+B1? in the treat:ent of ;atients &ith +-%S and
+-%S8related co:;leA# + do"<le8<lind, ;lace<o8controlled trial# $ /ngl . )ed !E'D
."lN @!D>?F!E(8D#
# 5e&is 5%, +:in S, *ivin *-, 5iet:an 0S# /A vivo Cidov"dine >+B1? treat:ent of
*%@O <one :arro& ;rogenitors ca"ses decreased steady state :itochondrial %$+
>:t%$+? and increased lactate ;rod"ction H":# /A; 1oAicol (00N(@F !D@8'5#
5# Kie<"rtC K%, Seidllin ), 5a:<ert .S, %ollis R, Reich:an R, ,alentine 1# /Atended
follo&8"; of ne"ro;athy in ;atients &ith +-%S and +-%S related co:;leA treated
&ith dideoAyinosine# . +c="ir -::"no %efic Syndro: !EE(N 5F60 66#
6# Re )*, Bon -, )onari 0, Gorini R, Schiavone 0, Gi<ellini %, et al. %r"g fail"re
d"ring H-,8! treat:ent# $e& ;ers;ectives in :onitoring dr"g resistance# $e&
)icro<iol (00@N (6>?F 058!@#
D# Salsa 1, ,eiga 3, 0ina )/# 2ral controlled8release dosage for:s# -# *ell"lose ether
;oly:ers in hydro;hilic :atrices# %r"g %ev -nd 0har: !EEDN(@FE(E8@'#
'# Korsen:eyer R7, 0e;;as $+# )acro:olec"lar and )odeling +s;ects of S&elling8
*ontrolled Syste:s editor# )ansdorf S# B#, Rose:an 1# .# )arcel %ekker -nc#, $e&
6orkN !E'@#;# DD#
E# +lder:an %+# + revie& of cell"lose ethers in hydro;hilic :atrices for oral
controlled8release dosage for:s# -nt . 0har: 1ech 0rod )fr# !E'N5F!6E#
!0# Rasso"l %, Sanaj ), /ffat 3, )asso"d S, 3ati:a +# 0re;aration of gelatin
:icros;heres containing lactic acid8 /ffect of crosslinking on dr"g release, +cta
;har:# (005N55F5D86D#
!!# Santos H, ,eiga 3, 0ina )/, So"sa ..# *o:;action, co:;ression and dr"g release
characteristics of Aanthan g": ;ellets of different co:;ositions# /"r . 0har: Sci
(00 3e<N (!>(8@?F(D!8'!#
D
!(# +l8Saidan S), Krishnaiah 6S, Satyanarayana ,, Bhaskar 0, Karthikeyan RS#
0har:acokinetic eval"ation of g"ar g":8<ased three8layer :atriA ta<lets for oral
controlled delivery of highly sol"<le :eto;rolol tartrate as a :odel dr"g# /"r .
0har: Bio;har: (00 $ovN 5'>@?F6ED8D0@#
!@# 1o<yn )., Staniforth .$, Baich&al +R, )c*all 17# 0rediction of ;hysical
;ro;erties of a novel ;olysaccharide controlled release syste:# -# -nt . ;har: !EE6
3e< (EN!('>!8(?F!!@8((#
!# ,endr"scolo *7, +ndreaCCa -3, Ganter .5, 3errero *, Bresolin 1)# Ganthan and
galacto:annan >fro: M. scabrella? :atriA ta<lets for oral controlled delivery of
theo;hylline# -nt . 0har: (005N(E6F !8!!#
!5# Saria:ornsak 0, 1hira&ong $, 7eera;ol 6, $"nthanid ., S"ngthongjeen S# S&elling
and erosion of ;ectin :atriA ta<lets and their i:;act on dr"g release <ehavio"r# /"ro
. of ;har: <io;har: (00DN6DF (!!8E#
!6# Saravanak":ar ), ,enkates&ara:"rthy $, %hachina:oorthi %, 0er":al 0#
/Atended release :atriA ta<lets of Stav"dineF 3or:"lation and in vitro eval"ation#
+sian jo"rnal of ;har:ace"tics (0!0N >@?F (!E8(@#
!D# 0raja;ati 0H, $ak": ,,, 0atel *$# 3or:"lation and eval"ation of floating :atriA
ta<let of stav"dine# -nt . 0har: -nvestig# (0!( +;rN (>(?F'@8E#
'
E
-,. REMAR0 OF THE )UIDE
1he a<ove infor:ation and literat"re has <een verified and &as fo"nd to <e correct#
1he ;resent st"dy &ill <e carried o"t "nder :y s";ervision and g"idance#
--. --.- NAME AND DESI)NATION
OF THE )UIDE
--.+ SI)NATURE
DR. M. S. SRINATH
M.PHARM ,Ph.D
DIRECTOR SET(S COLLE)E OF
PHARMAC*
DEPT. OF PHARMACEUTICS,
S/14S *255/G/ 23 0H+R)+*6,
S#R#$+G+R, %H+R7+%8 5'000(#
--./ NAME AND DESI)NATION
OF CO.)UIDE
--.1 SI)NATURE

.............
--.2 HEAD OF THE
DEPARTMENT
--.3 SI)NATURE
Pr"#. S. P. THA00ER M. Pharm.
PROFESSOR AND HEAD,
DEPT.OF PHARMACEUTICS,
S / 14s *255/G/ 23 0H+R)+*6,
S# R# $+G+R, %H+R7+%85'000(#
-+. -+.- REMAR0 OF THE
PRINCIPAL

1he a<ove :entioned infor:ation is correct and -
reco::end the sa:e for a;;roval#

-+.+ SI)NATURE

Dr. V. H. 0UL0ARNI M.Pharm, Ph.D.,
PROFESSOR AND PRINCIPAL,
S / 14s *255/G/ 23 0H+R)+*6
S# R# $+G+R,
%H+R7+%85'000(#

!0