(310f) Polymorph Selection By Continuous Precipitation
AIChE Annual Meeting
2017
2017 Annual Meeting
Separations Division
Solid Form Selection: Cocrystals, Salts, Solvates, Polymorphs, and Beyond
Tuesday, October 31, 2017 - 9:45am to 10:05am
Due to polymorphic variation in mechanical, electrical, stability, bioavailability and physicochemical properties, there always exists an optimal polymorph for a given application. Sometimes, a thermodynamically metastable form is preferred. In these cases, intelligent process design must be utilized to produce the desired polymorph. By judiciously selecting a solvent, temperature, inlet supersaturation, and residence time, one can typically produce a pure, preferred polymorph in a continuous crystallization process regardless of the polymorphâs thermodynamic stability. Design rules exist to guide the process engineer for systems in which heterogeneous nucleation and size independent linear crystal growth are the dominant mechanisms of solid deposition from solution. [1] Here, we hypothesize that these findings remain qualitatively true in precipitative systems in which homogeneous nucleation and/or agglomeration are also important crystal growth mechanisms. This hypothesis is supported by our recent experiments in which we continuously produce metastable forms of agglomerative CaCO3. We have also extended the population balance analysis to include systems in which agglomeration is significant. Here we report these experiments and calculations and explain the implications for general polymorphic systems that exhibit significant agglomeration.
[1] Farmer, T. C., Carpenter, C. L., & Doherty, M. F. (2016). Polymorph selection by continuous crystallization. AIChE Journal, 62(9), 3505-3514.