Characterisation and solid-state behaviour of Sunitinib Malate in its various crystalline forms

Abstract

The aim of this project was to study and characterise the solid- state behaviour of sunitinib malate in its various crystalline forms. Sunitinib malate is an active pharmaceutical ingredient (API) used for the treatment of renal cell carcinoma, neuroendocrine tumours and imatinib- resistant gastrointestinal stromal tumours. This API is characterised by low bioavailability as it has pH- dependent solubility, where as pH increases, the solubility decreases. A solubility screen was carried out to compile information regarding the behaviour of the API in different solvents and solvent mixtures. This was followed by a polymorph screen. All polymorph samples were analysed through optical and hot stage microscopy, IR- spectroscopy and powder X-ray diffraction (PXRD). From the proposed solid- state characterisation techniques, three samples exhibited changes. Definite confirmation of formation of three different polymorphs or solvates was given based on PXRD data. Cocrystal screening was carried out to study the effect of different stoichiometric ratios on cocrystal formation. Eight GRAS molecules were chosen throughout the author’s B.Sc. and 1: 1- API: coformer samples were synthesised. For this project, identical conformers were chosen and 1: 2- API: coformer samples were prepared. All prepared samples where characterised using hot stage microscopy, IR- spectroscopy and PXRD. It was deduced that different stoichiometric ratios allow the formation of different products. This was confirmed through analysis of PXRD data where there was the formation of a total of seven new crystalline forms. The solid- state behaviour was also tested through solubility screen of the various crystalline forms of the API, in various pH, mainly pH 1.06, 4.01 and 7.03. Such screen confirmed that methods of solid- state chemistry and crystal engineering, lead to changes in physical properties without altering the structure of the API. An overall improvement in all polymorphs and cocrystal samples was noted. This suggests that various crystalline forms of the API might be more effective for treatment purposes, as the higher the solubility, the more the bioavailability of the drug.