冻干是获得稳定的,即用型制剂不稳定的药物产品的关键生产过程。一些制剂可能需要添加药物特异性的赋形剂,例如稳定剂,缓冲剂和填充剂,以支持蛋糕外观并确保药物产品的长期稳定性。在包括冷冻,初次和二次干燥在内的每个阶段,冻干工艺参数的优化都很重要,因为这些参数会直接影响工艺效率(缩短循环时间)和产品性能(饼状外观和均匀的水分含量)。制剂的几个参数,包括活性药物成分的性质,赋形剂,溶剂系统和容器密闭性,决定了冻干的成功。开发,扩大规模,冻干周期的转移具有挑战性;因此,对与制剂,冻干过程和冻干机设计有关的关键参数的全面理解可以设计出优质的药品。在实验室和商业规模的冻干机之间成功进行冻干循环转移的一种方法是使用药瓶传热系数和冰板测试来确定最大升华速率。这篇综述提供了冻干过程的一般概述,并从工业角度讨论了配方,过程优化,容器密封系统,放大原理和药品质量属性的几个关键考虑因素和产品开发方面。对与制剂,冻干过程和冻干机设计有关的关键参数的全面理解可以设计出优质的药品。在实验室和商业规模的冻干机之间成功进行冻干循环转移的一种方法是使用样品瓶传热系数和冰板测试来确定最大升华速率。这篇综述提供了冻干过程的一般概述,并从工业角度讨论了配方,过程优化,容器密闭系统,放大原理和药品质量属性的几个关键考虑因素和产品开发方面。对与制剂,冻干过程和冻干机设计有关的关键参数的全面理解可以设计出优质的药品。在实验室和商业规模的冻干机之间成功进行冻干循环转移的一种方法是使用药瓶传热系数和冰板测试来确定最大升华速率。这篇综述提供了冻干过程的一般概述,并从工业角度讨论了配方,过程优化,容器密闭系统,放大原理和药品质量属性的几个关键考虑因素和产品开发方面。在实验室和商业规模的冻干机之间成功进行冻干循环转移的一种方法是使用药瓶传热系数和冰板测试来确定最大升华速率。这篇综述提供了冻干过程的一般概述,并从工业角度讨论了配方,过程优化,容器密闭系统,放大原理和药品质量属性的几个关键考虑因素和产品开发方面。在实验室和商业规模的冻干机之间成功进行冻干循环转移的一种方法是使用药瓶传热系数和冰板测试来确定最大升华速率。这篇综述提供了冻干过程的一般概述,并从工业角度讨论了配方,过程优化,容器密闭系统,放大原理和药品质量属性的几个关键考虑因素和产品开发方面。
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Lyophilization of Small-Molecule Injectables: an Industry Perspective on Formulation Development, Process Optimization, Scale-Up Challenges, and Drug Product Quality Attributes.
Lyophilization is a pivotal manufacturing process to obtain a stable drug product that is unstable as a ready-to-use formulation. Some formulations may require the addition of drug-specific excipients such as stabilizers, buffers, and bulking agents to support the cake appearance and ensure long-term stability of the drug product. Optimization of the lyophilization process parameters at each stage including freezing and primary and secondary drying is important because these parameters can have a direct impact on the process efficiency (shortened cycle time) and product performance (cake appearance and homogeneous moisture content). Several parameters of the formulation, including properties of the active pharmaceutical ingredient, excipients, solvent system, and container closure, determine the success of lyophilization. Development, scale-up, and transfer of the lyophilization cycle are challenging; hence, a comprehensive understanding of the critical parameters related to the formulation, lyophilization process, and lyophilizer design allows designing a quality drug product. One approach for a successful transfer of the lyophilization cycle between the laboratory and commercial-scale lyophilizer is using vial heat transfer coefficient and ice slab test to establish a maximum sublimation rate. This review provides a general overview of the lyophilization process and discusses several key considerations and product development aspects of formulation, process optimization, container closure system, scale-up principles, and drug product quality attributes from the industrial viewpoint.