Cocrystals of Modafinil-Nicotinic acid:A Novel Cocrystal for Enhanced Bioavailability

In this work, we are the first to identify and report pharmaceutically effective cocrystals of poorly soluble drug Modafinil (MOD) using crystal engineering approach. A multi-component system of MOD with nicotinic acid (NIC) as coformer at 1:1 molar ratio was prepared to simultaneously improve solubility, dissolution and bioavailability by applying liquid assistant grinding technique. Nicotinic acid as a potential coformer for cocrystal preparation was predicted using a novel approach of Hansen Solubility Parameter (HSP) group contribution method. Various evaluation parameters pertaining to confirm cocrystal formation like Fourier Transformer Infrared spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD), and Field Emission Scanning Electron Microscopy (FESEM) were carried out. Further effect of precipitation inhibitors (HPMC) on in-vivo bioavailability enhancement was also studied. MOD-NIC cocrystals formation was confirmed by integrating results of instrumental techniques. Aqueous solubility and in-vivo pharmacokinetic study proved 5.96 and 1.88 times higher bioavailability respectively in case of prepared cocrystals compared to MOD alone whereas bioavailability further increased by 2.72 times when these cocrystals were administered in presence of precipitation inhibitor. Hence, solid state manipulation was successful for preparing modafinil cocrystals as a potential method for illustrating several properties. The concept of cocrystals coupled with precipitation inhibitors significantly enhanced the bioavailability of modafinil.