Polymorphism and Crystallization of Famotidine

Abstract

Famotidine crystallizes in two different polymorphic forms: the metastable polymorph B and the stable polymorph A. In this work, solid characterization for both polymorphs has been conducted in detail. The solubility, metastable zone width and interfacial energy of both polymorphs in different solvents have been measured. The influence of solvent, cooling rate, initial concentration, nucleation temperature, and seeding on polymorphism has been investigated. Experimental results show that the nature of polymorph that crystallizes from solution depends on the initial concentration, solvent, cooling rate, nucleation temperature, and seeding strategy. In addition, the polymorphic transformation from polymorph B to polymorph A in slurry is slow, and yet can be accelerated by increasing temperature and seeding with polymorph A.