Crystal structure of indapamide determined from powered diffraction data

Indapamide is used in the treatment of hypertension. In the European Pharmacopoeia it is specified that indapamide may contain up to 3 wt.% of water. On the basis of the results of thermal (TGA, DSC), DVS and X-ray powder diffraction analyses it has been supposed that this feature arises from the fact that indapamide exists in the form of a non-stoichiometric hydrate. The water molecules are only weakly and reversibly bound into the crystal structure. The major framework of the crystal structure, built of indapamide molecules, remains practically unchanged upon dehydration and/or hydration processes. In order to prove this hypothesis and understand the hydration-dehydration behavior, the as yet unknown crystal structure of indapamide needed to be determined. Since it was not possible to grow any adequate single crystals, we decided to solve the structure from laboratory X-ray powder diffraction data. The solved structure confirmed the hypothesis of weakly bound water in the voids between the indapamide molecules and also served as a basis to evaluate and explain the relative humidity dependence of the unit cell parameters of indapamide.