卡托普利片工艺放大关键质量属性关键工艺参数.docx

摘要QbD是质量源于设计（QualitybyDesign）的简称是一种科学的、基于风险的、全面的和先进的药品开发方法强调通过对产品属性和生产工艺的理解通过设计和控制来保证产品的质量属性。本文运用QbD理念以某生产企业为例详细阐述了QbD在卡托普利片空白颗粒法工艺放大中的应用及作用。首先根据产品目标特性确定了卡托普利片的关键质量属性为标示量、溶出度、卡托普利二硫化物、含量均匀度、硬度、脆碎度；其次针对该部分关键质量属性及空白颗粒法工艺放大的工艺与过程进行分析、理解并应用风险评估确定了工艺放大的关键工艺参数为颗粒水分、制粒参数、整粒参数、混合参数；第三通过风险评估、实验设计、过程分析等技术手段和方法及现有知识详细说明了关键质量属性及关键工艺参数间的函数关系进而确定了卡托普利片空白颗粒法工艺放大的设计空间与控制策略。最后在设计空间内进行生产操作关键质量属性指标均控制在内控标准范围内经统计产品一次合格率等指标确认利用QbD可以改善和保证卡托普利片空白颗粒法工艺放大的效益及最终产品的质量。关键词：QbD；卡托普利片；工艺放大；关键质量属性；关键工艺参数ApplicationofQbDintheProcessScaleUpoftheBlankGranulationMethodinCaptoprilTabletManufacturingtoEnhanceandEnsuretheImprovementofEfficiencyandFinalProductQualityAbstractQbDtheabbreviattionfor"QualitybyDesign"isascientificrisk-basedholisticandproactiveapproachtopharmaceuticalproductdevelopmentwhichemphasizesontheunderstandingofproductattributesandprocesscontrolandensuringthequalityattributesofaproductthroughdesignandcontrol.ThisthesiswiththemanufacturingofcaptopriltabletasanexmapleillustratedtheapplicationandbeneficialeffectofQbDinthescale-upoftheblankgranulationprocess.FirstbasedonthetargetproductprofiletheCriticalQualityAttributesofcaptopriltabletwereconfirmedi.e.dissolutioncaptoprildisulfidecontentuniformitystrengthandfriability.SecondthroughtheanalysisandunderstandingoftheCriticalQualityAttributesandtheprocessforthescale-upoftheblankgranulationmethodtheCriticalProcessParametersforthescale-upoftheblankgranulationprocessofcaptoprilwereidentifiedi.e.moisturecontentofparticlesandtheprametersofgranulationandfinalmix.ThirdthroughapplyingriskevaluationDOEandPATtechnologiesandmethodsandotheravailableknowledgeandinformationthefunctionoftheCriticalQualityAttributesandtheCritialProcessParameterswasderived.Inturnthedesignspaceofthescale-upofblankgranulationprocesswasdetermined.Lastlythe