The use of solution calorimetry with micellar solvent systems for the detection of polymorphism

The presence of multiple polymorphic forms in seven batches of raw material of a model compound having poor wettability properties (cimetidine) was studied by solution calorimetry. Due to the large number of polymorphic forms described in the literature ('Gazz. Chim. Ital., 109 (1979) 535'; 'J. Pharm. Sci., 73 (1983) 1436'; 'J. Pharm. Biomed. Anal., 3 (1985) 303') and its poor wettability characteristics, cimetidine was chosen as a model compound to illustrate the possible use of solution calorimetry in the detection of polymorphism using surfactant systems as solvents for dissolution. Due to the closeness of the melting points of the different polymorphic forms of cimetidine, DSC was not the best investigational tool. As initially suspected, the measurement of enthalpy of solution values in water of the cimetidine batches was not possible. However, the use of sodium dodecyl sulfate (SDS) and polysorbate 20 (Tween 20(R)) at concentrations above their respective cmc values permitted the detection of significant differences in enthalpy of solution among several batches. The presence of different polymorphic forms was confirmed by microscopy, X-ray powder diffractometry, and Fourier transform infrared spectroscopy.