Executive Summary : | The revised project proposal focuses on the development of multi-drug cocrystals of anti-diabetic agents, specifically Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i), for the management of Type 2 diabetes mellitus (T2DM). The study aims to improve the physical and chemical properties of these agents, which are often associated with SGLT2i's. The proposal proposes preparing drug-drug cocrystals from SGLT2i and DPP4i, aiming to improve their physical and chemical properties. Sub-chronic oral toxicity studies in rodents will be performed, along with the preparation of oral solid dosage formulations. A comparative bioavailability study of cocrystal tablets in human volunteers will be performed, and pharmacometrics study will be conducted to predict the dose range for the cocrystals using pharmacokinetic modeling and simulation. The study aims to address the issues associated with the arrangement of supramolecular synthons in the crystal lattice, which could lead to the development of new solid forms of these drugs with modulated physicochemical properties. This multimodal treatment approach could be more advantageous than fixed-dose combination (FDC) or co-administration of SGLT2i and DPP4i. |