EVALUATION AND FORMULATION OF MICROSPONGES OF ATORVASTATIN

SYNOPSIS SUBMITTED TO

UTTARAKHAND TECHNICAL UNIVERSITY,DEHRADUN IN THE PARTIAL FULFILLMENT

OF
BACHELOR DEGREE OF PHARMACY BY DIVYA BAHUGUNA
SUPERVISOR. PROF.(DR.) Mr. VINEY CHAWLA CO-SUPERVISOR. ASST.PROFESSOR Miss.SHIKHA YADAV

CONTENT

INTRODUCTION
1

Introduction Literature Survey Drug Profile Polymer Profile Aim and Objective Method Evaluation References

Conventional topical formulations are designed to work on the outer layers of the skin. When the active ingredients of these formulations are released upon application, a highly concentrated layer of active ingredient is produced that is rapidly absorbed. Recently, there has been considerable interest in the development of novel microsponge based drug delivery systems to achieve targeted and sustained release of drugs (Kaity et al., !1!". #icrosponges are polymeric delivery systems consisting of porous microspheres that are mostly used for e$tended topical administration of a variety of active ingredients such as emollients, fragrances, essential oils, sunscreens, and anti%infective, anti%fungal, and anti%inflammatory agents. #icrosponges offer many advantages such as delivering the active ingredients at minimum dose, enhanced stability, reduced side effect and modified drug release profile.

 A !"#$"%&s '( )i*r's+'#%&s '!&r '$,&r $&*,#'-'%i&s "# &-i!&r. s.s$&)s 1" #icrosponges offer better control of drug release than microcapsules. #icrocapsules cannot usually control the release rate of the active pharmaceutical ingredients (&'(". )nce the wall is ruptured, the &'( contained within the microcapsules will be released. " #icrosponges show better chemical stability, higher payload and easier formulation compared with liposomes. *" (n contrast to ointments, microsponges have the ability to absorb skin secretions, therefore, reducing greasiness and shine from the skin. )intments are often aesthetically unappealing, greasy and sticky, resulting in lack of patient compliance. P'$&#$i"- (&"$/r&s '( )i*r's+'#%& r/% &-i!&r. s.s$&)s 1" #icrosponges show acceptable stability over p+ ranging from 1 to 11 and at high temperatures (up to 1*!,C". . #icrosponges e$hibit good compatibility with various vehicles and ingredients. *. #icrosponges have high entrapment efficiency up to -! to .!/ without drying.

Li$&r"$/r& S/r!&.
((rit et al. ( !!!" 'hosphated cross%linked guar gum was prepared for colon%specific drug delivery. 0uar gum cross%linked with increasing amounts of trisodiumtrimetaphosphate to reduce its swelling properties for use as a vehicle in oral delivery formulations, especially drugs aimed at locali1ing in the distal portions of the small bowel. 2welling of guar gum in artificial 0( fluids was reduced from 1!! 1 !% fold to 1!%*-%fold depending on the amount of cross linker used. 3ee et al.( !!!" )rganic acids like succinicacid, tartaricacid and citricacid were used as e$cipients in matri$ granules to modify the drug release for colon% specific drug delivery (4ykanen et al. 1555". &mylose% 6thylcelluese film coatings obtained from organic%based solvents were investigated as potential vehicles for colon drug delivery. (n this method amyulose% butanol dispersion and ethycellulose in ethyllacttate7ethnol7propanol with dibutylsebacate as plastici1er were mi$ed in various proportions and coated on -%&2& pellets to achieve desired thickness. 8he drug release regulating parameters are thickness of coating and ratio of amylose to ethylcelluese. 8he release of drug is irrespective of the solvent used for coating. 9ormulation containing 1 part amylase and 1 part ethylcelluose of coating thickness, 1-/ 8W0, gives desired release profiles of -%&2& for colon targeting.

 9ude et al. ( !!:" &n oral colonic drug delivery system of -%&2& was developed using combination of p+dependent, time%based and en1yme degradable approaches. 8he pellets were coated with three functional layers i.e. the outer 6udragit3*!;%-- layer for protection against 0( fluids, the intermediate layer of ethyl cellulose to inhibit the drug release during passage through the small intestine and the inner layer of pectin for swelling and en1yme%degradation. (n vitro release studies indicated that the coated pellets completely protected the drug release in !.1# +Cl while the drug release was delayed for three to four hours in p+ ..< phosphate buffer. .

Dr/% Pr'(i-&
A$'r!"s$"$i# ((44" marketed by 'fi1er as a calcium salt under the trade name Li+i$'r,is a member of the drug class known as statins, which are used primarily for lowering blood cholesterol and for prevention of events associated with cardiovascular disease &torvastatin was first synthesi1ed in 15<- by =ruce Roth, an alumnus of 2aint >oseph?s @niversity, while he was working for the 'arke%;avis Company (since acAuired by Warner%3ambert and the 'fi1er Company". &lthough &torvastatin was the fifth drug in the class of statins to be developed, clinical trials showed that &torvastatin caused a more dramatic reduction in 3;3%C than the other statin drugs. 9rom 155. to !1 under the trade name 3ipitor, &torvastatin became the world?s best%selling drug of all time, with more than B1 - billion in sales over appro$imately 1C.years.When 'fi1er?s patent on 3ipitor e$pired on 4ovember *!, !11,generic &torvastatin became available in the @nited 2tates. (nitially, &torvastatin was manufactured only by generic drugmakers 3aboratories. Watson 'harmaceuticals and (ndia?s Ranba$y

S.s$&)"$i* (IUPAC) #")& (*R,-R"%:%D %(C%fluorophenyl"%*%phenyl%C% (phenylcarbamoyl"%-%propan% %ylpyrrol%1%ylE%*,-% dihydro$yheptanoic acid Clinical data Tr" & #")&s AHFS0Dr/%s.*') M& -i#&P-/s Li*&#*& "$" 3ipitor,&torva monograph a.!!!C@2 ;aily #edFlink

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P,"r)"*'1i#&$i* "$" Bi'"!"i-"2i-i$. M&$"2'-is) H"-(--i(& E3*r&$i'# A )i#is$r"$i'#4 &torvastatin may be used in combination with bile acid seAuestrants and e1etimibe to increase the reduction in cholesterol levels. +owever, (t is not recommended to combine statin drug treatment with certain other cholesterol%lowering drugs, particularly fibrates, because this may increase the risk of myopathy%related adverse effects. C'#$r"i# i*"$i'#s4

1 / +epatic % CH'*&C 1C h =ile

&ctive liver diseaseF cholestasis, hepatic encephalopathy, hepatitis, and Iaundice

@ne$plained elevations in &28 or &38 levels

'regnancyF &trovastatin may cause fetal harm by affecting serum cholesterol and triglyceride levels, which are essential for fetal development.

=reastfeedingF 2mall amounts of other statin drugs have been found to pass into breast milk, although &torvastatin has not been studied, specifically.

P'-.)&r Pr'(i-&
& polymer, natural or synthetic is a substance that is combined with a drug or other active agent to release drug in a pre%designed manner1. 8he development of 4;;2 has been made possible by the various compatible polymers to modify the release pattern of drug ,*. Choice of polymers always suffering from the problems of non%biocompatible, non%biodegradable and e$pensive and this problem can solve with a polymer of different properties. Y&"r '( i#$r' /*$i'# E/ r"%i$ Gr" & 15-C 6udragit 3 1 .6udragit 2 1 .15-5 6udragit 6 1 .15.1 6udragit 6 1!! 15.< 6udragit R3 1!! 6udragit R2 1!!

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AIM OF THE PRESENT RESEARCH WORK4 8he present study was aimed at developing and characteri1ing microsponge based, for the treatment of (=2 to achieve following obIectsF 8o overcome potential side effects of &terovastatins and enhancing their therapeutic effectiveness. 8o develop superior formulation with pronounced targeting potential of drugs to colon as compared to conventional delivery systems. PLAN OF WORK 6$haustive 3iterature survey through Iournals and e%Iournal. 'rocurement of ;rug, and 6$cipient. 'reformulation studies 'reparation and optimi1ation of microsponges. ;evelopment of colon specific formulation. (n vitro and stability studies of promising formulations.

E!"-/"$i'#
Measurement of particle size Morphology and Surface topography Production yield and entrapment efficiency P'6 &r 7-r". i((r"*$i'# (7RD)4 In vitro release studies, release kinetics and mechanism

R&(&r&#*&s
1"(rit 0liko%Kabir, =oris Hagen, &brahem Rubinstein et al. ( !!!" 'hosphated cross linked guar for colon%specific drug delivery (. 'reparation and physicochemical characteri1ation. >ournal of Controlled Release .*F 1 1%1 :. "3ee 9.2iew, &bdul W.=asit, and #ichael 4ewton > ( !!!" 8he potential of organic%based &mylose%6thyl cellulose film coatings as oral colon%specific drug delivery system. &&'2 'harm2ci8ech 1(*"F 1-1-%1- 1. *" #ohini Chaurasia, #anish K, Chourasia, 4itin K. >ain et al. ( !!.". Cross%linked guar gum microspheresJ & Kiable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer. &&'2 'harm 2ci 8ech :(*"F 61%65. C" #unIeri ), Collett >+ and 9ell >8 (155:". +ydrogel beads based on amidated pectins for colonspecific drug deliveryF the role of Chitosan in modifying drug release. >ournal of Controlled Release C.F :*% :<.