Discrimination of polymorphic forms of a drug product by localized thermal analysis

In chemical processing, it is important to distinguish between and identify polymorphic forms. We demonstrate the novel use of scanning thermal microscopy (SThM) and localized thermal analysis to distinguish and identify polymorphic forms of the drug cimetidine. These forms cannot be resolved by classical bulk thermal analysis. SThM reveals a sample consisting of a 50 : 50 mixture of the polymorphs contains regions of different thermal conductivity, corresponding to the different polymorphs. Localized thermal analysis of small volumes of pure polymorphic samples (approximately 50 microm3) shows that the origin of the thermal conductivity contrast lies, at least in part, with the presence of a surface water layer on the more hydrophilic polymorph.