褪黑素双层控释片制备及其在Beagle犬体内的药动学.docVIP

褪黑素双层控释片制备及其在Beagle犬体内的药动学 中国新药与l临床杂志(ChinJNewDrugsClinRem),2006年7月,第25卷第7期?527? [文章编号]1007—7669(2006)07—0527—04 褪黑素双层控释片制备及其在Beagle犬体内的药动学 张涛一,杨勇一,周远大3,陈兰,一,曾志,一,邓履红, (1.西南药业股份有限公司药物研究所,重庆400038;2.重庆太极医药研究院,重庆4~015; 3.重庆医科大学附属第一医院临床药理研究室,重庆400016) [关键词]褪黑激素;药动学;狗;控释制剂 [摘要]目的:研制褪黑素双层控释片,并研究其药动学.方法:以羟丙甲基纤维素,硬脂酸为骨架材料,采 用固体分散技术和双层压片工艺,制备褪黑素双层控释片.6只Beagle犬随机交叉单剂灌服褪黑素双层控释 片(6mg)或参比制剂(3mg),以高效液相色谱法测定血浆中褪黑素浓度,3P97程序推算药动学参数.结果: 灌服受试制剂和参比制剂后,t{h分别为(3.3±s0.9)和(1.2±0.5)h,c一分别为(8±5)和(1l±4)IxgL～, ￡～分别为(1.0±0.4)和(0.50±0.20)h,AC分别为(38±16)和(25±8)Ixg?h?.结论:研制的褪黑素双 层控释片具有速释和缓释特性. [中图分类号]R965;R969.1;R971.3[文献标识码]A Preparationofmelatonincontrolled-releasebilayertabletsanditspharmacoki- neticsinBeagledogs ZHANGTao,YANGYong卫,ZHOUYuan—da,CHENLan卫,ZENGZhi卫,DENGLti—hong卫 (1.1nstituteofSouthwestPharmaceuticalCompanyLtd.,CHONGQING400038,China;2.ChongqingTaijiAcade— myofMedicine,CHONGQING400015,China;3.DepartmentofClinicalPharmacology,theFirstAffiliatedHos— pitalofChongqingMedicalUniversity,CHONGQING400016,China) [KEYWORDS]melatonin;pharmacokinetics;dogs;controlledreleasepreparation [ABSTRACT]AIM:Topreparemelatonincontrolled—releasebilayertabletsandstudyitspharmacokineticsin Beagledogs.METHODS:Melatonincontrolled—releasebilayertabletswerepreparedbythesoliddispersion methodandtwicecompressiontechnology,usingHPMCandstearicacidasthematrixmateria1.Inarandomized, crossoverdesign,asingleoraldoseofmelatonincontrolled—releasebilayertablets(6mg)orreferencepreparation (3mg)wasgivento6beagledogs,andthenplasmaconcentrationsofmelatoninweredetectedbyHPLCmethod withthepharmacokineticparameterscalculatedby3P97pharmacokineticprogram.RESULTS:Thetkc., ￡ ACoftestsreferencepreparationwere(3.3±s0.9)US(1.2±0.5)h,(8±5)US(11±4)Ixg?,(1.0±0.4) US(0.50±0.20)h,(38±16)US(25-4-8)Ixg?h?L～,respectively.CONCLUSION:Theformulatedmelatonin sustained—releasebilayertabletsexhibitsustainedreleaseandrapidreleasecharacteristicsnvitroandnvivo. 【收稿日期】2005—12—0l【接受日期】2006—04—30 【作者简介】张涛(1966一),男,四川资中人,教授级高级工程师,硕士,重庆太极医药研究院副院长,西南药业股份有限公司