·226·药学学报ActaPharmaceuticaSinica2007，42(2)：226—230微孑L渗透泵片的药物传递机制赵学玲1，李强1，龚显峰1，李三鸣24(1．黑龙江大学制药科学与工程系，黑龙江哈尔滨150080；2．沈阳药科大学药学院，辽宁沈阳110016)关键词：微孔渗透泵；渗透压；体外释放；盐酸曲马多中图分类号：R943文献标识码：A文章编号：0513—4870(2007)02—0226—05Thedeliverymechanismofmicro—porousosmoticpumptabletsZHAOXue—lin91，LIQian91，GONGXian—fen91，LISan—min92+(J．DepartmentofPharmaceuticalScienceandEngineering，HeilongjiangUniversity，Harbin150080，China；2．SchoolofPharmaceuticalScience，ShenyangPharmaceuticalUniversity，Shenyang110016，China)Abstract：Toinvestigatethedeliverymechanismofmicro—porousosmoticpumptablets(MPOP)，takingtramadolhydrochloride(TR)asthemodeldrug，tramadolhydrochloridemicro—porousosmoticpumptablets(TRMPOP)werepreparedwithcompressiblestarchasdiluent，celluloseacetateascoatingmaterial，polyethyleneglycol400aspore—formingagents．TheequilibriumsolubilityandosmolalityofTRweredetermined．Theeffectsoffillersintabletcores，coatinglevels，andosmoticpressuresofreleasemediaonexpansionbehaviorofpreparationsweredescribed．Theinfluencesofthecategory，osmolality，andpHvalueofreleasemedia，releasemethods，andreleaseconditionsonreleasecurvesoftabletswereevaluated．Basedonseveralmodels，thedeliverypatternofTRMPOPwasfitted．TheequilibriumsolubilityinwaterandosmolalityofTRwere(775．8±17．7)g·L～and4．036Osmol·kg～，respectively．Duringthedrug—releaseperiod，itwasobservedthatthetabletsexpandedmarkedlyinresponsetotheexpansioncharacteristicsofcompressiblestarchandtheosmoticpressuredifferenceacrossthemembrane．Whenosmoticpressureofreleasemediaincreased，thesignificantchangeoftheequilibriumsolubilityofTRwasnotfound，butthereleaseratesofTRMPOPdecreasedsignificantly．ThedeliveryratewasnotinfluencedbythepHofreleasemediums，dissolutionmethodsandpaddlestirringrates．Thedrugreleaseprofileconformedtothemodelofzeroorderin8h．Thepore—formingagentsweredissolvedinreleasemedium，whichcausedmicro—pores．Theexpansionoftabletsmadethesizeof—micro—poresbigger，andthenthedrug—releasingporeswereobtained．ItwasprovedthatthedriversofdrugdeliveringfromTRMPOPweremainlythedifferenceofosmoticpressure，andsecondlythedifferenceofsolubility．TRMPOPwerethecontrolled—releasepreparation．Keywords：micro—porousosmoticpump；osmoticpressure；invitrodissolution；tramadolhydrochloride口服渗透泵片以渗透压为驱动力，以零级释放动力学为释药特征，能在一定的时间内以恒定的释药速率释放药物，释药速率一般不受释放介质pH、收稿日期：2006-05—15．‘通讯作者Tel／Fax：86—24—23986258，E—mail：li_sanming@sina．com搅拌速度及胃肠蠕动、食物等因素的影响，是理想的一种口服控释制剂¨’2；。口服渗透泵片包括药物、渗透促进剂(药物也可以作为渗透促进剂)和其他辅料制成的片心，以及半渗透膜包衣。初级口服渗透泵片主要分为两种类型，一种为半渗透膜用适当方法(如激光)开一细万方数据赵学玲等：微孔渗透泵片的药物传递机制孔；另一种为半渗透膜含水溶性致孔剂，遇水后致孔剂从膜中沥出形成微孔。药物在渗透促进剂溶解后形成的渗透压作用下，从细孑L或微孔中释放。后者称为微孔渗透泵(micro—porousosmoticpumps，MPOP)，避免了制备释药孑L的操作过程¨。o。本文以盐酸曲马多(tramadolhydrochloride，TR)为模型药物，对自制的盐酸曲马多微孑L渗透泵片(tramadolhydrochloridemicro—porousosmoticpumps，TRMPOP)的药物传递机制进行探讨。材料与方法材料与仪器TR(石家庄市第一制药厂)；可压性淀粉(湖州展望药业有...
