Production-Scale Particle Design of a Pharmaceutical Intermediate
Production-Scale Particle Design of a Pharmaceutical Intermediate
复制标题
药物中间体的生产规模颗粒设计
DOI：
10.1021/cg0300376
复制
发表时间：
2004
影响因子：
3.8
通讯作者：
J. Tschernjaew
中科院分区：
文献类型：
--
作者：
B. Braun;H. Groen;J. Tschernjaew
制药和生命科学领域的产品需求由于与新配方相关的新药开发和应用而迅速变化。本文介绍了设计最佳结晶工艺的最新进展，在设计阶段结合了客户对结晶产品物理性能的需求，特别是粒度和粒度分布。简单的实验室规模的批量结晶实验进行提取成核，生长和聚集的相关动力学参数，并确定进一步的机制，如解聚和磨损。聚集，也考虑成核和生长，通过人口平衡模型模拟，而解聚被认为是通过定量测定的颗粒间的力量。使用这种新的设计路线，生产规模的结晶过程，包括连续操作的空气喷射结晶器与集成的澄清区成功地委托。
Product requirements within the pharmaceutical and life sciences sector change rapidly due to new drug developments and applications linked to new formulations. This paper presents recent developments in designing an optimal crystallization process incorporating, at the design stage, customer demands regarding the physical properties of the crystalline product, notably particle size and particle size distribution. Simple laboratory-scale batch crystallization experiments were performed to extract the relevant kinetic parameters of nucleation, growth, and aggregation and to identify further mechanisms such as disaggregation and attrition. Aggregation, considering also nucleation and growth, was simulated via population balance modeling whereas disaggregation was considered by quantitative determination of the interparticle forces. Using this new design route, a production-scale crystallization process comprising a continuously operated air-jet crystallizer with an integrated clarification zone was successfully commissioned.