Mechanochemistry vs. solution growth: striking differences in bench stability of a cimetidine salt based on a synthetic method

Abstract

A mechanochemically prepared solvated salt of the archetypal blockbuster drug cimetidine exhibits significantly different bench stability to an analogous material made in solution. Samples obtained from solution are stable for weeks at room temperature and 45 °C, but mechanochemically made ones readily desolvate and convert to a new polymorph of non-solvated salt. While mechanochemistry becomes increasingly popular in synthesising drug solid forms, this work illustrates that it can have a profound effect on material stability.