过程分析技术在多晶型原料药结晶工艺开发中的应用.解读.docVIP

摘 要 研究目的：本文希望通过了解以往和现行的结晶技术，理解并掌握过程分析技术，将过程分析技术引入到原料药的结晶工艺的开发和控制中，以增强工艺的稳健性，确保生产出需要的晶型。 研究方法：本文首先通过文献搜集法，搜集国内外结晶工艺的发展状况和过程分析技术的应用，总结出过程分析技术应用的重要性。再通过案例研究法，具体的说明过程分析技术是如何运用到结晶工艺的开发中。 研究结果: 通过对几种结晶工艺开发的总结，详细的说明了过程分析技术在多晶型原料药结晶工艺开发中的应用，叙述了过程分析技术在工艺开发中的优势。证明了过程分析技术的应用能有效降低风险，增加结晶工艺的稳健性，确保生产出需要的晶型。 研究结论：通过实时的测量关键质量、过程中的物料和最终产品的质量，PAT的应用能确保原料药的质量。 关键词：多晶型原料药；在线分析技术；原料药质量Applications of Process Analytical Technology to Crystallization Process Development of Polymorphic Drug Substances Abstract Background: Different crystalline forms of the API（active pharmaceutical ingredients） can have different chemical and physical properties, these properties will directly affect the stability of the API, solubility, and bioavailability, thus affecting the quality, safety, and efficacy of the drug products. How scientific and rational design and control of the crystallization process of the polymorphic drug substances could manufacture the product consistently to meet the quality requirements for the crystalline form became the challenges that pharmaceutical companies needed to face. Research Purposes: Understand and master PAT（process analysis technology） by analysis of the crystallization technology used in the past and now, and introduce PAT to the development and control of the API crystallization process to enhance the process robustness to ensure production of the desired polymorph. Research Methods: The development status and the application of crystallization process and PAT in the API crystallization process in the home and abroad were collected by literature search to sum up the importance of PAT tool. And explain how PAT is applied to the crystallization process of development through case study. Results: The procedures of the application of PAT in the API crystallization were specified in detail by the summary of the crystallization process development of several types of polymorphic forms. The advantage of PAT in the process development was also analyzed. The results s