Calorimetric determinations and theoretical calculations of polymorphs of thalidomide

The analysis of the thermograms of thalidomide obtained for the two reported polymorphs alpha and beta by differential scanning calorimetry (DSC) shows some inconsistencies that are discussed in the present work. The conception of a new polymorph form, named beta*, allowed us to explain the observed thermal behavior more satisfactorily. This new polymorph shows enantiotropy with both alpha and beta polymorphs, reflected in the unique endotherm obtained in the DSC-thermograms, when a heating rate of 10 degrees C/min is applied. Several additional experiments, such as re-melting of both polymorph forms, showed that there is indeed a new polymorph with an endotherm located between the endotherms of alpha and beta. IR, Raman, and powder X-ray permit us to characterize the isolated compound, resulting from the re-melting of both polymorph forms. Mechanical calculations were performed to elucidate the conformations of each polymorph, and ab initio quantum chemical calculations were performed to determine the energy of the more stable conformers and the spatial cell energy for both polymorphs alpha and beta. These results suggested a possible conformation for the newly discovered polymorph beta*. (C) 2006 Elsevier B.V. All rights reserved.