琥珀酸美托洛尔脉的冲控释微丸的制备.doc

琥珀酸美托洛尔脉冲控释微丸的制备 琥珀酸美托洛尔脉冲控释微丸的制备 黄桂华,杨晓,王德凤,席延卫(1,山东大学药学院,山东济南250012;2.烟台中医院药剂科,山东烟台264oo0) 摘要:目的制备琥珀酸美托洛尔脉冲控释微丸并考察体外释放影向因素.方法采用挤出滚圆法制备载药丸芯,使用水溶 胀性材料为内包衣溶胀层,乙基纤维素水分散体为外包衣控释层制备脉冲控释微丸,并考察溶胀层材料类型,溶胀层和控释 层包衣增重对药物释放的影响.结果药物通过控释层衣膜破裂而释放,溶胀层材料类型,溶胀层和控释层包衣增重对脉冲 控释微丸的释药时滞和释药速率均有显着性影响.结论采用低取代羟丙基纤维素(L-HPC)与羟丙基甲基纤维素(HPMC)以 一 定比例混合作为溶胀层,乙基纤维素(Ec)水分散体为控释层制备的脉冲控释微丸,当内包衣层增重为17%和外包衣层增重 为16%时,在模拟人体内胃肠道pH值变化条件下达到了时滞为4.5h,时滞后1.5h累积释药80%以上的脉冲释药效果. 关键词:琥珀酸美托洛尔;脉冲释药系统;微丸;低取代羟丙基纤维素;羟丙基甲基纤维素;乙基纤维素水分散体 中图分类号:R943.41文献标识码:A文章编号:1001—2494(2005)23—1801—04 Preparationofmetoprololsuccinatepulsafilecontrolled-releasepellets HUANGGui.hua,YANGXiao2,WANGDe.feng,XIYan-wei(1.SchoolofPharmacy,ShandongUniversity,Jinan250012,China;2.Yantai ChineseTraditionalMedicineHospital,Yantai264000,china) ABSTRACT:OBJECT1VETopreparethemetoprololsuecinate(MS)pulsatilecontrolled-releasepellets(MS-PCRP),METHODSThe MS-loadMpelletspreparedbyextrusion—spheronizationtechnologywerecoatedwithswellingmaterialastheinnercoatingswellinglayerand ethyleelluloseaqu~usdispersionastheoutercoatingcontrolledlayer.Theeffectsofthecoatingmaterialsoftheswellinglayer,thecoatinglevel oftheswellinglayerandthecontrolledlayerontherelea~ofMSfromMS-PCRPwereevaluated.RESULTSThedrugreleasewastriggered whilethemembraneofthecontrolledlayerwasraptured.Thecoatingmaterialoftheswellinglayer.thecoatingthicknessleveloftheswelling layerandthecontrolledlayerhadsignificanteffectonthelagtimeandthereleaserateofMSfromPCRP.CONCLUSIONTheMS-PCRP. withalagtimeof4.5handmolethan80%releasedwithinfollowing1.5hunderthesimulatedgastro-intestinalpHconditions.areprepared byusinglow-substitutedhydmxypmpylcelluloseastheinnerswellinglayerwith17%(weight)coatingthicknesslevelandethylcelluloseaque— OUSdispersionastheoutercontrollinglayerwith16%(weight)coatingthicknessleve1. KEYWORDS:metopmlolsuccinate;pulsatile;pellets;L-HPC;HPMC;ethylcelluloseaqueousdispersion 时辰药理学的研究表明,一些疾病如心血管疾 病,哮喘,关节疼痛的发生发作均存在时辰节律的变 化l1J.这些疾病症状常常在凌晨加剧,患者通常无 法及时服药预防疾病发作或减轻症状.脉冲给药系 统是根据时辰药理学和时辰治疗学原理设计的新型 控释给药