Characterization and selective crystallization of famotidine polymorphs.
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 and the temperature of nucleation on polymorphism has been investigated. Results show that the nature of polymorph that crystallizes from solution depends on the initial concentration of the solution, solvent, cooling rate, and the temperature of nucleation. Polymorph B preferentially crystallizes only at high concentrations. When acetonitrile or methanol is used as solvent, cooling rate can affect the polymorph of product only at high concentrations. While water is used as solvent, cooling rate has no effect on the polymorph of product, and nucleation temperature is found to be the predominant controlling factor. The effect of crystallization conditions on the polymorph of famotidine can be mainly attributed to the conformational polymorphism. Finally the "polymorphic window" for famotidine crystallized from aqueous solution has been described.
Lu
Jie
J
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637722. lujie@ntu.edu.sg
Wang
Xiu-Juan
XJ
Yang
Xia
X
Ching
Chi-Bun
CB
D003460:Crystallization; D004055:Differential Thermal Analysis; D015738:Famotidine / Q000008:administration & dosage / Q000737:chemistry*; D007536:Isomerism; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013500:Surface Tension; D013696:Temperature; D014961:X-Ray Diffraction
D012997:Solvents; D015738:Famotidine