Thermal analysis and calorimetric methods in the characterisation of polymorphs and solvates

The definitions and thermodynamic background for interpreting thermal analysis data are presented in this review. Most drug substances and excipients which have been reported to display polymorphism and pseudo-polymorphism are referenced. The influence of experimental parameters and substance parameters on thermoanalytical data are presented. The limits and advantages of thermal methods and combined techniques are discussed. Examples describing the use of solution calorimetry and microcalorimetry are given. Thermal methods are unique in providing knowledge of thermodynamic data, for producing modifications and for distinction between polymorphs, solvates and impurities. The methods require only a small amount of material. However, for complex polymorphic behaviour, other techniques have to be used in addition. Kinetic data can be calculated in some situations. Thermal analysis methods are generally limited to routine quantitative analysis of polymorphism. Microcalorimetric techniques are useful complements for the study of polymorphism and pseudo-polymorphism and in certain cases for quantitative determinations.