Crystal Form Control and Particle Size Control of RG3487, a nicotinic α7 receptor partial agonist.

This paper describes the crystal form control and particle size control of a drug candidate, RG3487. Based on polymorph screen results and form stability investigation, the crystal form control was achieved by appropriate crystallization solvent selection which consistently produced the desired solid form. The particle size control was successfully accomplished by tuning key crystallization parameters, including HCl addition temperature, agitation rate, MTBE addition time and hold times. As a result, three batches of drug substances in 500g scale with the right crystal form and intentionally different particle sizes were produced for downstream formulation development.