Polymorph selection by continuous crystallization

Abstract

This article is motivated by a remarkable observation reported recently by Myerson, Trout, and co‐workers that continuous crystallization is capable of producing metastable polymorphs in stable steady‐state operation. We explain why this phenomenon occurs and give simple design rules for reproducing it in other polymorphic systems. A linear stability analysis gives simple functions of parameters for which one can continuously produce thermodynamically metastable products based only on the relative polymorph dynamics. We demonstrate agreement with two sets of experimental data; L‐glutamic acid grown from aqueous solution and p‐aminobenzoic acid also grown from aqueous solution. For many polymorphic compounds, engineering a process to produce a desired polymorph is as simple as finding a reasonable operating point for the continuous mixed‐suspension mixed‐product removal crystallization process (temperature, residence time, initial supersaturation, etc.) according to the rules reported in this article. © 2016 American Institute of Chemical Engineers AIChE J, 62: 3505–3514, 2016