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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,amountofcrosslinkingagentandpercentageofdrugloadinginordertooptimizeprocessvariablesondrugencapsulationef?ciency,releaserates,sizeandmorphologyofthemicrospheres.A24fullfactorialdesignwasemployedtoevaluatethecombinedeffectofselectedindependentvariablesonpercentageofdru
5、greleaseat5h(response).Regressionmodelswereusedfortheresponseanddatawerecomparedstatisticallyusingtheanalysisofvariance(ANOVA).Grafting,interpenetratingnetworkformationandchemicalstabilityofthecapecitabineafterencapsulationintomicrosphereswascon?rmedbyFourierinfraredspectra(FTIR).Differe
6、ntialscanningcalorimetry(DSC)andX-raydiffractometry(XRD)studiesweremadeondrug-loadedmicrospherestoinvestigatethecrystallinenatureofdrugafterencapsulation.Resultsindicatedamorphousdispersionofcapecitabineinthepolymermatrix.Scanningelectronmicroscope(SEM)con?rmedsphericalshapesandsmoothsur
7、facemorphologyofthemicrospheres.Meanparticlesizeofthemicrospheresasmeasuredbythelaserlightscatteringtechniquerangedbetween82and168m.Capecitabinewassuccessfullyencapsulatedintosemi-IPNmicrospheresandpercentageofencapsulationef?ciencyvariedfrom79to87.Invitroreleasestudiesw
