液相层积法制备兰索拉唑肠溶微丸的工艺研究

64Vol.6No.420087ChineseJournalofPharmaceuticsJul.2008p.133:2008–01–07(1981,(),,,[e-mail];(1969),(),,,,,Tel.[phone],[e-mail]200804013308110016L9(34)OPADRYYS17006EudragitL30D5590R94A(±)2[[[34(2,2,2)2]]]H+/K+ATP1992,[1-2][3]1JHQSartoriusBS110S752ZRD6BHPMC5cpsOPADRYYS17006EudragitL30D5522.12.1.1HPMC3g60mL134614g500600µm5min600700µm:360.6mL·min-1,29Hz2.1.215g5%(YS17006)4%[4]2.1.3EudragitL30D5510g10mLPEG60000.3g0.6g0.6g10mLEudragitL30D5530min15g456h2.22.2.12.2.21g(θ)θ[5]2.2.3(%)/×100(%)/×100%2.3HPLCDiamonsilC18(150mm×4.6mm5µm)640360515[6]pH7.3284nmA=2.199104ρ3.535103r=0.999910400mg·L-150mg25mL2mL25mL2.32.3.1413530MethodA7240.1mol·L-1500mL75r·min-11h25mL0.45µm306nm[7]0.1mol·L-1200400nmA2.7710-2ρ+1.9110-2r=0.9995210mg·L-12.3.265.4g28.2g12g4L37475mL10304560min286650nmpH6.8[7]pH6.8200400nmpH6.8A3.3710-2ρ+4.4210-2r=0.9998525mg·L-133.15cpsHPMC600700µm1HPMCHPMC5%HPMC600700µmHPMCHPMC5%‹Loadingratio;„24/28MeshcutyieldFig.1EffectofHPMCamountondrugloadingratioandyieldoflansoprazolecoregranules13663.2[8]pH4%20%2pH6.8020406080100020406080100120t/minw(cumulativedissolution)/%‹NoNaHCO3;„m(NaHCO3)m(lansoprazole)=13;{m(NaHCO3)m(lansoprazole)=11Fig.2EffectofNaHCO3/lansoprazoleratioonthedissolutionoflansoprazolefromentericcoatedpellets3.33(600700µm)76.2%HPMC112190.9%89.7%HPMCHPMC11aNotalc;bm(talc):m(HPMC)=1:3;cm(talc):m(HPMC)=1:1;dm(talc):m(HPMC)=2:1Fig.3Effectoftalc/HPMCratioontheyieldoflansoprazolepellets41373.43(A)(B)(C)33L9(34)600700µmyield,Y(loadingratio,L)(roundness,θ)12Table1FactorsandlevelsfortheorthogonalexperimentdesignFactorLevelAθ(pellets)/Bqv/mL·min-1Cfairflow/Hz1320.6262360.9293401.232Table2TheorthogonaldesignandexperimentalresultsNO.Aθ(pellets)/Bqv/mL·min-1Cfairflow/HzYw(yield)/%Lw(loadingratio)/%θroundness/°Y+Lθ111184.583.615.4152.7212283.286.317.2152.3313378.182.219.3141.0421289.893.915.2168.5522381.690.118.8152.8623179.779.419.6139.5731381.684.417.4148.6832180.880.318.7142.4933277.278.220.3135.1148.7156.6144.9153.6148.2152.0142.0138.5147.5R11.618.17.12(A)(B)(C)3BACA2B1C2360.6mL·min-129Hz391.6%87.9%3.5(YS17006)EudragitL30D554LPZ138615%pH6.820%25%220%15%„20%c25%Fig.4Dissolutionprofilesoflansoprazoleentericcoatedpelletswithdifferentcoatingamount3.6335390%pH6.890%Table3PropertiesofthreebatchofpelletsamplesBatchw(yield)/%w(loadingratio)/%w(0.1mol·L-1HCl)/%w(pH6.8buffer)/%191.494.31.8395.62292.393.21.5697.13391.095.12.1295.91{Batch1;„Batch2;cBatch3;ReferenceFig.5Dissolutionprofilesofthreebatchesoflansoprazoleentericcoatedpelletsandreferencepellets41394a.HPMC5HPMC11(A)(B)(C)BACA2B1C2360.6mL·min-129Hzb.(YS17006)EudragitL30D5590%[1]BARRADELLLB,FAULDSD,MCTAVISHD.Lansoprazole,areviewofitspharmacodynamicandpharmacokineticspropertiesanditstherapeuticefficacyinacid-relateddisorders[J].Drugs,1992,44:225250.[2]YUKAKOI,HARUMIA,KAORIU,etal.Effectofadsorbentsontheabsorptionoflansoprazolewithsurfactant[J].InternationalJournalofPharmaceutics,2005,289:6977.[3]AlBINK,FRANCV.Preformulationinvestigationofthenovelprotonpumpinhibitorlansoprazole[J].DrugDevelopmentandIndustrialPharmacy,2000,26(7),781783.[4]CHENJivn-ren,SHREVEPORTLA.Stableoralpharmaceuticaldosageforms:US,7094426B2[P].20040426.[5].[M].:,2001:534.[6],,.HPLC[J].,2006,41(7):538.[7]TheUnitedStatesPharmacopeialConvention.USPharmacopeia30/NationalFormulary25[M].30thed.Rockville:theBoardofTrustees,2007:2452.[8]MAKINOT,TABATAT,HIRAIS.Stabilizedpharmaceuticalcompositioncomprisingabenzimidazolecompound,itsproductionanditsuseasanantiulceragent:European,0237200A2[P].19820213.PreparationoflansoprazoleentericcoatedpelletsbyliquidphaselayeringLIZhen,DINGPing–tian,HAOTang–naCHENLi–yun(SchoolofPharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China)1406Abstract:ObjectiveTopreparelansoprazoleentericcoatedpelletsandinvestigateinvitrodrugrelease.MethodLansoprazolepelletswerepreparedbyliquidphaselayeringmethodwithafluidizedbedequipment,theoptimalprocessingparameterswereobtainedbyorthogonalexperimentdesign.ThereafterthelansoprazolepelletswerecoatedwithOPADRYYS17006andEudragitL30D55,andeffectsofcoatinglevelondrugreleasecharacteristicswasstudied.ResultTheoptimizedenteric-coatedpelletswassphericalwithsmoothsurfaceandthepelletswereacidresistant.Incontrast,drugreleaseinartificialintestinalliquidwasrapidandcomplete.ConclusionThepreparationprocedureissimpleandfeasible,whichiseasytobescaledup.Keywords:pharmaceutics;entericcoatedpellets;liquidphaselayering;lansoprazole;fluidbed;drugrelease