Liquid-liquid phase separation in pharmaceutical crystallization

被引：11

作者：

Yu, Zai-Qun ^{[1
]}

Zhang, Fang-Kun ^{[2
]}

Tan, Reginald Beng Hee ^{[3
]}

机构：

[1] ASTAR, Inst Chem & Engn Sci Ltd, 1 Pesek Rd, Singapore 627833, Singapore

[2] Qingdao Univ Sci & Technol, Coll Automat & Elect Engn, 99 Songling Rd, Qingdao 266061, Shandong, Peoples R China

[3] Natl Univ Singapore, Dept Chem & Biomol Engn, 10 Kent Ridge Crescent, Singapore 119260, Singapore

来源：

CHEMICAL ENGINEERING RESEARCH & DESIGN | 2021年 / 174卷

关键词：

Crystallization; Liquid-liquid phase separation; Phase diagram; Seeding; Supersaturation control; OILING-OUT; 2-STEP MECHANISM; NUCLEATION; VANILLIN; CRYSTALS; PURIFICATION; BEHAVIOR; GROWTH; SYSTEM; SIZE;

D O I：

10.1016/j.cherd.2021.07.028

中图分类号：

TQ [化学工业];

学科分类号：

0817 ;

摘要：

Liquid-liquid phase separation (LLPS) during crystallization development of pharmaceuticals is being reported increasingly in recent years. It often causes quality issues such as failure of impurity reject and fragile morphology. In worst cases, crystallization cannot proceed at all after LLPS occurs. Many studies have been published on LLPS during crystallization and an analysis and synthesis of the current state-of-art is needed. In this review, recent advances in LLPS research will be summarized, including brief theoretical interpretations of LLPS, characteristics in phase diagrams and measurement methods for representative model systems, strategies to suppress LLPS, crystallization development in the presence of LLPS and options when direct crystallization fails due to LLPS. This review aims to provide a framework to deal with the occurrence of LLPS during crystallization development. (c) 2021 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.

引用

页码：19 / 29

页数：11

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