New findings on the solvent-mediated polymorphic transformation of famotidine

In this work, the solvent-mediated polymorphic transformation (SMPT) of famotidine (FMT) Form B to Form A was investigated experimentally in six different solvents to broaden the available knowledge on it and clear previous contradictions. It was found that among the examined solvents, FMT was only prone to SMPT in water. Therefore, the aqueous SMPT of FMT was investigated in depth. The main process parameters included solid loading, temperature, seeding and addition of a widely used pharmaceutical excipient and crystallization additive poly(vinyl pyrrolidone) (PVP). It was found that the denser the suspension was, the longer the transformation process took. However, at higher temperatures, the transformation rate increased considerably. Eventually, at 75°C and solid loading of 48 mg/mL, the decomposition of FMT occurred before SMPT finished. Interestingly, seeding did not decrease transformation time in merit but contributed to the elevation of transformation rate in the early stages of the SMPT process. Moreover, the addition of PVP to the suspension could completely hinder SMPT, and no Form A could be identified in the suspension.