Institute on Membrane Technology (ITM-CNR), Via P. Bucci Cubo 17/C, c/o University of Calabria, I-87030 Rende (CS), Italy.
J Pharm Sci. 2009 Dec;98(12):4902-13. doi: 10.1002/jps.21785.
This article describes a modification of the conventional membrane crystallization technique in which a membrane is used to dose the solvent/antisolvent composition to generate supersaturation and induce crystallization in a drug solution. Two operative configurations are proposed: (a) solvent/antisolvent demixing crystallization, where the solvent is removed in at higher flow rate than the antisolvent so that phase inversion promotes supersaturation and (b) antisolvent addition, in which the antisolvent is dosed into the crystallizing drug solution. In both cases, solvent/antisolvent migration occurs in vapor phase and it is controlled by the porous membrane structure, acting on the operative process parameters. This mechanism is different than that observed when forcing the liquid phases through the pores and the more finely controllable supersaturated environment would generate crystals with the desired characteristics. Two organic molecules of relevant industrial implication, like paracetamol and glycine, were used to test the new systems. Experiments demonstrated that, by using antisolvent membrane crystallization in both configurations, accurate control of solution composition at the crystallization point has been achieved with effects on crystals morphology.
本文描述了一种对常规膜结晶技术的改进，该技术利用膜来投加溶剂/反溶剂组成物以产生过饱和度并在药物溶液中诱导结晶。提出了两种操作配置：（a）溶剂/反溶剂分相结晶，其中溶剂以比反溶剂更高的流速除去，从而促进相转变以产生过饱和度；（b）反溶剂添加，其中将反溶剂计量加入结晶药物溶液中。在这两种情况下，溶剂/反溶剂迁移都发生在气相中，并且受多孔膜结构控制，从而作用于操作工艺参数。这种机制与迫使液体通过孔时观察到的机制不同，更精细可控的过饱和环境将生成具有所需特性的晶体。使用两种具有重要工业意义的有机分子，如对乙酰氨基酚和甘氨酸，来测试新系统。实验表明，通过在两种配置中使用反溶剂膜结晶，可以在结晶点精确控制溶液组成，并对晶体形态产生影响。
