EAD Physico-chimie Industrielle du Médicament (EA4066), Faculté de Pharmacie, Université Paris Descartes, 4, Avenue de l'Observatoire, 75006 Paris, France.
J Phys Chem B. 2012 May 10;116(18):5568-74. doi: 10.1021/jp302508g. Epub 2012 May 1.
Enantiomer resolution is much sought after for pharmaceutical applications, because many optically active drug molecules have only one pharmaceutically active enantiomer. Although it is always possible to force separation, it will come at a cost. The present method, based on thermodynamics, provides a relatively easy approach to investigate whether separation can be thermodynamically spontaneous. A topological phase diagram of the binary enantiomer system at 0.5 mol-fraction is constructed as a function of temperature and pressure after analysis of pressure and heat related quantities. It is demonstrated that for ibuprofen, an optically active analgesic, the racemate is the only stable solid form; the phase relationship between the racemate and the conglomerate is analogous to dimorphism with overall monotropy in pure chemical compounds.
对映体拆分在制药领域有很大的需求，因为许多手性药物分子只有一个具有药理活性的对映异构体。虽然可以强制进行分离，但这会产生成本。本方法基于热力学，提供了一种相对简单的方法来研究分离是否可以在热力学上自发进行。通过分析压力和热相关量，构建了二元对映体系统在 0.5 摩尔分数下的拓扑相图作为温度和压力的函数。结果表明，对于布洛芬这种具有光学活性的镇痛药，外消旋体是唯一稳定的固体形式；外消旋体和齐聚物之间的相关系类似于纯化合物中的同质多晶现象，具有整体单调性。
