Thermal characterization of some polymorph solvates of the anti-inflammatory/anti-cancer sulindac

Solvates of sulindac were obtained by crystallization from acetone, chloroform, dichloromethane and tetrahydrofuran, but not from water, methanol, ethanol and propanols, acetonitrile and ethyl acetate and were studied by thermal (differential scanning calorimetry - DSC, thermogravimetry - TGA and thermomicroscopy - HSM) and spectroscopic (micro-Raman, SEM, X-EDS) analysis. It emerged from the thermal analysis that the samples thus obtained are not simple solvates or pseudo-polymorphs, but rather polymorph solvates, where the new form could be evidenced only after desolvation in controlled conditions, since the desolvation and polymorph transition processes occur together and in the thermogram the endotherms overlap. Desolvation, that is accompanied by decoloration of the sample from orange to yellow, enabled calculation of the solvate stoichiometry by the TGA parameters. The polymorph obtained from desolvation of the acetone solvate displays different thermal parameters from those obtained with chloroform, dichloromethane and tetrahydrofuran solvates. According to the solvents employed for crystallization, these thermal events leave sulindac in the form I or both I and II, outlining the very complex nature of the solid state of this drug. A new unsolvated polymorph form was directly obtained applying the technique of the quasi emulsion solvent diffusion (QESD). These results could open new perspectives in the use of the anti-inflammatory/anti-cancer sulindac in terms of formulation and mode of delivery and release.