Crystal form control and particle size control of RG3487, a nicotinic α7 receptor partial agonist

Abstract

This paper describes solid form control and particle size control of RG3487, a nicotinic receptor partial agonist. Four crystal forms were identified by polymorph screen under ∼100 varying conditions. Form A and Form B are anhydrates, while Forms C and D are solvates. Forms A, which is enantiotropically related to Form B, is the more thermodynamically stable form under ambient conditions and the desired form selected for clinical development. The crystal form control of Form A was achieved by crystallization solvent selection which consistently produced the desired form. Several process parameters impacting particle size of Form A in the final crystallization step were identified and investigated through both online and offline particle size measurement. The investigation results were utilized to control crystallization processes which successfully produced Form A with different particle size in 500g scale.