(324e) Effect of Lattice Incorporated Impurities on Crystallization of a Pharmaceutical Compound. a Case Study in Early Development.
AIChE Annual Meeting
2023
2023 AIChE Annual Meeting
Separations Division
Foreign Species and Crystallization: Impurity Rejection, Additives, Dopants, etc.
Monday, November 6, 2023 - 4:45pm to 5:03pm
Presented herein is a pharmaceutical case study describing how relatively low levels of impurities exerted a dramatic impact on the success and robustness of the crystallization by affecting the API solubility, seed step, yield and apparent crystallization kinetics. In addition, the extent and severity of encrustation during the crystallization was directly linked to the presence of impurities. The underlying mechanism responsible for these adverse effects was found to be formation of solid solutions between the API and impurities, in concert with a very efficient crystal packing of the API from where slight disturbances to the crystal lattice afforded significant thermodynamic changes. This case study provides an important example of how lattice incorporated impurities have the ability to interfere with basic thermodynamic and kinetic parameters, which without a priori detection can turn a well-behaved isolation into a process failure.