Studies On Bupivacaine Loaded Sustained-release Microspheres

Bupivacaine(Bupi) has been widely used fOr clinics since 60th. It is considered arelatively safe and effective drug fOr providing spinal anesthesia, epidural anesthesia,brachial nerve blockage and postoperative ease pain. Side effects about cardiovascularand nerve center system have been observed due to the accumulation of bupivacaineplasma concentration. Moreover, the effect that bupivacaine en1arge local vascularwill reduce anesthetic effective duration. Therefore, in order to prolong the anestheticaction, minimize side effects and decrease frequency of administration. the suitablesustained-reIease microspheres containing bupivacaine were prepared using Humanserum albumin (HSA)and poly(lactic-co-glycolic) acid(PLGA) as carriers and theprilling theory, preparing technology, stability, release characteristics in vilro,pharmacodynamics, pharmacokinetics, irritation, degradation of bupivacainemicrospheres in vivo were evaluated.The emulsifing heat-denatured method has been used to prepare Bupivacainehuman serum albumin microspheres(Bupi-HSA-MS)using unifOrm design and theeffect of preparing condition on particle size, re1ease rate. drug content and drugentrapment have been researched. The resu1t show that particle size was effected bystirring rate evidently (P<0.0l), the drug content was effected by drug/ HSAconcentration ratio distinctive1y (P<0.0l), the washing times and the volume ofwashing solvent could affect the drug content and drug entrapment efficiency, as wellas decrease burst effect of Bupi-HSA-MS. The experiment of release declared that thereIease rate was faster with smaller particle size and release mode of Bupi-HSA-MScould be described by Higuchi equation better with large particle size, where as itcould be described by First order equation better with small particle size.A new preparing method, high voItage electric electrostatic heat-denaturedmethod was established in order to increase the drug entrapment efficiency, decreasethC bllfst CffeCt sfld lffipFOVC thC FCpfodllCtlofl f3tlo OfpfCp＆f3tlofl．ThC fCSlllt ShOWCdhat the span of particle size was decreaseu from．98 to 0．52,the drua entrapme川efficiency was Increasedfrom 50．87％to gi．62％with new method comparing withemulslfing heat刁enaturect method。 Hlghperformance caplll叼 electrophoresls(HPCE)was establlshedtodetermined the release ofB叩l－MS with agood linear overthe range ofZ．0～64．opg／ml(r＝0．999996)．The average recovery was 02．24t3．160,the RSD of withinday and between day were．45土0．43％,1．06上0．29％respectively and thedetermination limit was 0．5卜g／ml．HPCE has many advantage,such as rapidity,lowCOSt,SllPllClty,SSSSltlVlty,lfld SO Off． In order to prolong the release ofbuplvacalne further more,buplvacalne PLGAmlcrospheres(Bupl－PLGA－MS)was prepared with emulslfying－solvent evaporationmethod．Orthogonal design was used to optimize the technological condition withresult of higher drug content,higher drug entrapment efficiency and low burst e地ct．The In vltro release profile ofbuplvacalne PLGA mlcrospheres could be dlscrlbed byirst－orderklnetlc equation．Thehalheleasetlme(t；；,)ofPLGA－MS was 169．16mln．W冰fCSS,山e他lftlffiC OffCIC3SCtl／,Ofofopfl31 bUplVdC8lflC pOW此f W3S扣．85ffilfl．The result ofdrug release experiment with different drugcontent showed that the drugcontent could affect release mode ofBupl－PLGA－MS．The in vilro release profile ofBupi－PLGA－MS with low drug content(12．24O)could be described by Hlguchlequation basedondl地slon release and that ofBupl－PLGA－MS With high drugcontent(28．92O)could be described by irst－order kinetic equation based ondissoMlon anddesorptlon． ThC CXpCflffiCflt Ofstsblllty lfldlC3tC thst thC ChCffilC31 3lid physiC31 pfopCYtlCS OfBupi－HSA－MS and Bupi－PLGA－MS were stable afterplaced Indifferent conditionwith different storage time． Thepharmacoklnetlcs andpha...