Novel interpenetrating network chitosan-poly(ethylene oxide-g-acrylamide

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1、InternationalJournalofPharmaceutics324(2006)103115Novelinterpenetratingnetworkchitosan-poly(ethyleneoxide-g-acrylamide)hydrogelmicrospheresforthecontrolledreleaseofcapecitabineSunilA.Agnihotri,TejrajM.Aminabhavi∗DrugDeliveryDivision,CenterofExcellenceinPolymerScience,KarnatakUniversity,

2、Dharwad580003,IndiaReceived30November2005;receivedinrevisedform3April2006;accepted28May2006Availableonline3June2006AbstractThispaperdescribesthesynthesisofcapecitabine-loadedsemi-interpenetratingnetworkhydrogelmicrospheresofchitosan-poly(ethyleneoxide-g-acrylamide)byemulsioncrosslinkingu

3、singglutaraldehyde.Poly(ethyleneoxide)wasgraftedwithpolyacrylamidebyfreeradicalpolymerizationusingcericammoniumnitrateasaredoxinitiator.Capecitabine,ananticancerdrug,wassuccessfullyloadedintomicrospheresbychangingexperimentalvariablessuchasgraftingratioofthegraftcopolymer,ratioofthegraft

4、copolymertochitosan,amountofcrosslinkingagentandpercentageofdrugloadinginordertooptimizeprocessvariablesondrugencapsulationefficiency,releaserates,sizeandmorphologyofthemicrospheres.A24fullfactorialdesignwasemployedtoevaluatethecombinedeffectofselectedindependentvariablesonpercentageofdru

5、greleaseat5h(response).Regressionmodelswereusedfortheresponseanddatawerecomparedstatisticallyusingtheanalysisofvariance(ANOVA).Grafting,interpenetratingnetworkformationandchemicalstabilityofthecapecitabineafterencapsulationintomicrosphereswasconfirmedbyFourierinfraredspectra(FTIR).Differe

6、ntialscanningcalorimetry(DSC)andX-raydiffractometry(XRD)studiesweremadeondrug-loadedmicrospherestoinvestigatethecrystallinenatureofdrugafterencapsulation.Resultsindicatedamorphousdispersionofcapecitabineinthepolymermatrix.Scanningelectronmicroscope(SEM)confirmedsphericalshapesandsmoothsur

7、facemorphologyofthemicrospheres.Meanparticlesizeofthemicrospheresasmeasuredbythelaserlightscatteringtechniquerangedbetween82and168m.Capecitabinewassuccessfullyencapsulatedintosemi-IPNmicrospheresandpercentageofencapsulationefficiencyvariedfrom79to87.Invitroreleasestudiesw