Compare drug release profiles.docx
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Compare drug release profiles.docx
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Comparedrugreleaseprofiles
Comparedrugreleaseprofilesofwaterpoorsolubledrugsfromanovelchitosanandpolycarbophilinterpolyelectrolytescomplexation(PCC)andhydroxylpropyl-methylcellulose(HPMC)basedmatrixtablets
ZhileiLu*,WeiyangChen,EugeneOlivier,JosiasH.,Hamman
DepartmentofPharmaceuticalSciences,TshwaneUniversityofTechnology,PrivateBagX680,Pretoria,0001,SouthAfrica
*Correspondingauthor:
ZhileiLu(Dr.)
DepartmentofPharmaceuticalSciences,
TshwaneUniversityofTechnology,
PrivateBagX680,
Pretoria,
0001,
SouthAfrica
(e-mail:
luzj@tut.ac.za)
Abstract
Theaimofthisstudywastocomparethedrugreleasebehavioursofwaterpoorsolubledrugsfromaninterpolyelectrolytecomplex(IPEC)ofchitosanwithpolycarbophil(PCC)andhydroxylpropylmethylcellulose(HPMC)basedmatrixtablets.Anovelinterpoly-electrolytecomplex(IPEC)ofchitosanwithpolycarbophil(PCC)wassynthesizedandcharacterized.WaterpoorsolubledrugsHydrochlorothiazideandKetoprofenwereusedinthisstudyasmodeldrugs.Polymers(includingPCC,HPMCK100MandHPMCK100LV)basedmatrixtabletsdrugcontrolledreleasesystemwerepreparedusingdirectcompressionmethod.TheresultsillustratePCCbased-matrixtabletsofferaswellingcontrolledreleasesystemforwaterpoorsolubledruganddrugreleasemechanismfromthismatrixdrugdeliverysystemcanbeimprovedbyadditionofmicrocrystallinecellulose(Avicel).Analysisoftheinvitroreleasekineticparametersofthematrixtablets,PCCbasedmatrixtabletsexhibitedsimilarorhigherdrugreleaseexponent(n)andmeandissolutiontime(MDT)valuescomparedtotheHPMCbasedmatrixtablets.ItdemonstratedthatPCCpolymercanbesuccessfullyusedasamatrixcontrolledreleasesystemforthewaterpoorsolublemodeldrugssuchashydroxylpropylmethylcellulose(HPMC).
1Introduction
Overthelastthreedecadesyears,astheexpenseandcomplicationsinvolvedinmarketingnewdrugentitieshaveincreased,withconcomitantrecognitionofthetherapeuticadvantagesofcontrolleddrugdelivery,greaterattentionhasbeenfocusedonthedevelopmentofnovelandcontrolledreleasedrugdeliverysystemstoprovidealong-termtherapeuticofdrugsatthesiteofactionfollowingasingledose(Mandal,2000;JantzenandRobinson,2002).Manyformulationtechniqueshavebeenusedto“build”thebarrierintotheperoraldosageformtoprovideslowreleaseofthemaintenancedose.Thesetechniquesincludetheuseofcoatings,embeddingofthedruginawax,polymericorplasticmatrix,microencapsulation,chemicalbindingtoion-exchangeresinsandincorporationintoanosmoticpump(CollettandMoreton,2002:
293).Amongdifferenttechnologiesusedincontrolleddrugdelivery,polymericmatrixsystemsarethemostmajoritybecauseofthesimplicityofformulation,easeofmanufacturing,lowcostandapplicabilitytodrugswithwiderangeofsolubility(Colombo,etal.,2000;JamzadandFassihi,2006).
Drugsreleaseprofilesfrompolymericmatrixsystemcaninfluencebydifferentfactors,butthetype,amount,andphysicochemicalpropertiesofthepolymersusedplayaprimaryrole(JamzadandFassihi,2006).Hydroxylpropyl-methylcellulose(HPMC)isthemostimportanthydrophiliccarriermaterialusedfororaldrugsustaineddeliverysystems(Colombo,1993;SiepmannandPeppas,2001).BecauseHPMCiswatersolublepolymer,itisgenerallyrecognizedthatdrugreleasefromHPMCmatricesfollowstwomechanisms,drugdiffusionthroughtheswellinggellayerandreleasebymatrixerosionoftheswollenlayer(Fordetal.,1987;Raoetal.,1990;Colombo,1993;Taharaetal.,1995;Reynolds,Gehrkeetal.,1998;Siepmannetal.,1999;SiepmannandPeppas,2001).However,diffusion,swellinganderosionaremostimportantrate-controllingmechanismsofcommercialavailablecontrolledreleaseproducts(LangerandPeppas,1983),themajoradvantagesofswelling/erosionHPMCbasedmatrixdrugdeliverysystemare:
(i)minimumthedrugburstrelease;(ii)thedifferentphysicochemicaldrugsreleaserateapproachaconstant;(iii)thepossibilitytopredicttheeffectofthedevicedesignparameters(e.g.shape,sizeandcompositionofHPMC-basedmatrixtablets)ontheresultingdrugreleaserate,thusfacilitatingthedevelopmentofnewpharmaceuticalproducts(Colombo,1993;SiepmannandPeppas,2001).
Interpolyelectrolytecomplexes(IPEC)areformedasprecipitatesbytwooppositelychargedpolyelectrolytesinanaqueoussolution,havebeenreportedasanewclassofpolymercarriers,whichplayanimportantroleincreatingneworaldrugdeliverysystems(PeppasandKhare,1993;Bergeretal.,2004).AvarietychemicalstructureandstoichiometryofbothcomponentsininterpolyelectrolytecomplexesdependsonthepHvaluesofthemedia,ionicstrength,concentration,mixingratio,andtemperature(Peppas,1986;DumitriuandChornet,1998;Bergeretal.,2004;Moustafineetal.,2005a).Chitosanisapositivelycharged(aminogroups)deacetylatedderivativeofthenaturalpolysaccharide,chitin(PaulandSharma,2000).Chitosanhasalreadybeensuccessfullyusedtoformcomplexeswithnaturalanionicpolymerssuchascarboxymethylcellulose,alginicacid,dextransulfate,carboxymethyldextran,heparin,carrageenan,pectinmethacrylicacidcopolymers(Eudragit®polymers)andxanthan(DumitriuandChornet,1998,Bergeretal.,2004,Sankaliaetal.,2007,MargulisandMoustafine,2006).
Inthisstudy,anovelpolymer-IPECbetweenchitosanandpolycarbophil(PCC)wassynthesized,characterizedandusedasdirectcompressedexcipientsinthematrixtablet.AlthoughithavebeenwellknownthatvariousIPEChavebeenusedasapolymercarriersindrugcontrolledreleasesystem(PeppasandKhare,1993,GarciaandGhaly,1996,Lorenzo-Lamozaetal.,1998,SoppirnathandAminabhavi,2002,Chenetal.,2004,Nametal.,2004,Moustafineetal.,2005b),IPECchitosanandpolycarbophilwasusedasapolymercarriershavebeeninvestigatedbyLuetal.,(2006,2007a,2007b,2008a;2008b).
TheaimofthisstudywastocompareinvitrowaterpoorsolubledrugsreleaseprofileofHPMCbasedmatricessystemtoPCCbasedmatricessystematsameformulation.WaterpoorsolublemodeldrugsHydrochlorothiazideandketoprofenwereusedinthisstudy.TwotypesHPMC(K100MandK100LV)andPCCpolymerswereusedindirectcompressedpolymersbasedmatrixdrugreleasesystem.TheresultsofthehydrationanderosionstudiesshowedPCCbasedmatrixsystemshavesuperiorswellingproperties.Drugreleaseexponent(n)ofeachformulationPCCbasedmatricestabletsarehigherthanHPMCbasedmatricestabletsatpH7.4buffersolutions.ItdemonstratedthatPCChashighpotentialtouseinpolymerbasedmatrixdrugcontrolledreleaseddeliveryforwaterpoorsolubledrugs.
2.Materialsandmethods
2.1Materials
Chitosan(WarrenChemSpecialities,SouthAfrica,DeacetylationDegree=91.25%),Polycarbophil(Noveon,Cleveland,USA),Hydroxylpropylmethylcellulose(MethocelK100M,K100LVPremium,ColorconLimited,Kent,England),Ketoprofen(ChangzhouSiyaoPharma.China),Hydrochlorothiazide(HuzhouKonchPharmaceuticalCo.,Ltd.China),Microcrystallinecellulose(Avicel,pH101,FMCcorporationNV,Brussels,Belgium),Sodiumcarboxymethylstarch(Explotab,EdwardMendellCo.,IncNewYork,USA).Allotherchemicalswereofanalyticalgradeandusedasreceived.
2.2Preparationofinterpolyelectrolytescomplexationbetweenchitosanandpolycarbophil(PCC)
Chitosan(30g)wasdissolvedin1000mlofa2%v/vaceticacidsolutionandpolycarbophil(30g)wasdissolvedin1000mlofa2%v/vaceticacidsolution.Thechitosansolutionwasslowlyaddedtothepolycarbophilsolutionunderhomogenisation(5200rpm,ZKA®,Germany)overaperiodof20minutes.Themixturewasthenmechanicallystirredforaperiodof1hourataspeedof1200rpm(HeidolphRZR2021,Germany).Thegelformedwasseparatedbycentrifugingfor5minat3000rpmandthenwashedseveraltimeswitha2%v/vaceticacidsolutiontoremoveanyunreactedpolymericmaterial.Thegelwasfreezedriedforaperiodof48hours(JouanLP3,France)andthelyophilisedpowderwasscreenedthrougha300µmsieve.
2.3Differentialscanningcalorimetry(DSC)
DSCthermogramsofthePCCwererecordedwithaShimadzuDSC50(Kyoto,Japan)instrument.Thethermalbehaviourwasstudiedbysealing2mgsamplesofthematerialinaluminiumcrimpcellsandheatingitataheatingrateof10oCperminundertheflowofnitrogenataflowrateof20ml/min.Thecalorimeterwascalibratedwith2mgofindium(Kyoto,Japan,meltingpoint156.4oC)ataheatingrateof10oCpermin.
2.4Fouriertransforminfrared(FT-IR)
Fouriertransforminfrared(FT-IR)spectraldataofthePCCpolymerwasobtainedonaFTS-175Cspectrophotometer(BIO-RAD,USA)usingtheKBrdiskmethod.
2.5Preparationofthematrixtablets
Inordertocomparethereleaseprofilesofwaterpoorsolubledrugsfrompolymerbasedmatrixtablets,monolithicmatrixtypetabletscontaininghydrochlorothiazideorketoprofenwerepreparedbycompressingamixtureoftheingredientswithvaryingconcentrationsofthePCC,HPMCK100MandHPMCK100LVasindicatedinTable1.Theingredientsofthedifferentformulationsweremanuallypre-mixedbystirringina1000mlglassbeakerfor30minuteswithaspatula.Aftertheadditionof0.05gofmagnesiumstearate(0.5%w/w),thepowdermasswasmixedfor10min.Thepowdermixturewascompressedusingarotatingtabletpress(Cadmach,India)fittedwithround,shallowpunchestoproducematrixtypetabletswitha6mmdiameter.
2.6Weight,hardness,thicknessandfriabilityoftablets
Weightvariationwastestedbyweighing20randomlyselectedtabletsindividually,thencalculatin
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