共无定形药物_新型单相无定形二元体系.docxVIP

共无定形药物———新型单相无定形二元体系*郭慧慧1苗娜娜1李腾飞2郝(1．中国药科大学药学院南京210009;2．君1高缘2张建军1＊＊中国药科大学中药学院南京210009)摘要共无定形药物是活性药物成分与其他小分子固体物质(药物或辅料)结合形成的具有单一玻璃化 转变温度的单相无定形二元体系。它作为一种新的药物固体形态，可能改善药物的溶解度、溶出速率、稳定性及生物利用度等理化性质，已成为药物研发的一种新途径。本文主要对共无定形药物的定义、形成机理、 制备方法、分析鉴别方法、物理化学稳定性以及溶解度和溶出速率进行综述，并对共无定形与固体分散体和共晶的比较进行了概述。关键词共无定形单相二元体系形成机理玻璃化转变温度稳定性中图分类号:TQ469;O641.3文献标识码:A文章编号:1005-281X(2014)02/3-0478-09PharmaceuticalCoamorphous———ANewlyDefinedSingle-PhaseAmorphous BinarySystem*GuoHuihui1MiaoNana1LiTengfei2HaoJun1GaoYuan2ZhangJianjun1＊＊(1．SchoolofPharmacy，ChinaPharmaceuticalUniversity，Nanjing210009，China;2．SchoolofTraditionalChineseMedicine，ChinaPharmaceuticalUniversity，Nanjing210009，China)AbstractPharmaceuticalcoamorphous，akindofsingle-phaseamorphousbinarysystem，isformedbetweenanactivepharmaceuticalingredient(API1)andanothersolidsmallmolecularcompound(API2orexcipient)．Asanewlydefinedsolidform，pharmaceuticalcoamorphoushasbeenonenewapproachfordrugresearchand development，duetoitsgreatpotentialintheimprovementofsolubility，dissolution，stabilityoreven bioavailability．Severalmethodscanbeusedforthepreparationofcoamorphousdrugs，includingquench-cooling，solventevaporationandmilling/cryo-milling．Inthispaper，thedefinition，preparation， physicochemicalcharacterizationandformationmechanismofpharmaceuticalcoamorphousareaddressed．The comparisonbetweencoamorphousandsoliddispersionorcocrystalsisalsopresented．Keywordscoamorphous;single-phasebinarysystem;formationmechanism;glasstransitiontemperature; stabilityContentsIntroductionOverviewofpharmaceuticalcoamorphous2.1Definitionandclassificationofcoamorphous2.2Comparisonbetweencoamorphousandsoliddispersion3ＲelationshipanddifferencesofcoamorphousandcocrystalFormationmechanisms1Typeofinteraction收稿:2013年7月，收修改稿:2013年9月，网络出版:2014年2月25日*国家“重大新药创制”科技重大专项项目(No．2011ZX09201-101-02)和“中央高校基本科研业务费专项资金”(No．JKP2011006)资助TheworkwassupportedbytheImportantNationalScience＆TechnologySpecificProjects(No．2011ZX09201-101-02)andFundamentalＲesearchFundsfortheCentralUniversities(No．JKP2011006)＊＊Corre