Solid state investigation and characterization of the polymorphic and pseudopolymorphic forms of indapamide

Solid state investigation and polymorphic screening of indapamide, a diuretic drug generally used for the treatment of hypertension was carried out. Substantial differences were obtained in the solid state properties of crystals confirming the existence of a polymorphic and three pseudopolymorphic forms of indapamide. Detailed methods of preparation of the polymorphs and pseudopolymorphs are described. X-ray powder diffraction (XRPD), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were employed for the characterization of different crystalline forms of indapamide. The stoichiometric ratio of solvents associated with the drug molecules in the pseudopolymorphic forms were calculated using TGA, nuclear magnetic resonance (NMR) spectroscopy and headspace gas chromatographic (HS-GC) analysis.