The effect of processing on the solid state characteristis of selected sulphonamides and their sodium salts, alone and as drug-salt composites

Abstract

The purpose of the research presented in this thesis was to produce metastable active pharmaceutical ingredients (API) by spray drying and to analyse, physico-chemically characterise these forms and develop strategies to enhance their physical stability. The solid state properties of two spray dried drugs and their sodium salt forms together with co-spray dried API/salt composites were investigated and compared to the unprocessed materials. The drugs investigated were the sulphonamide compounds, sulfadimidine and sulfathiazole. The compounds were spray dried from water, ethanol, acetone and mixtures of these organic solvents with water. The methods of analysis employed to characterise the resulting spray dried powders were conventional and modulated differential scanning calorimetry (DSC/MTDSC), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), attenuated total reflectance-FTIR (ATR-FTIR) and powder X-ray diffraction (PXRD). Surface properties were analysed by inverse gas chromatography (IGC) and morphology by scanning electron microscopy. Hygroscopic properties and water interactions were studied by dynamic vapour sorption (DVS).