In this work, we are the first to identify and report pharmaceutically effective cocrystals of the poorly soluble drug Modafinil (MOD) using a crystal engineering approach. A multi-component system of MOD with nicotinic acid (NIC) as the coformer at a 1:1 molar ratio was prepared to simultaneously improve the solubility, dissolution and bioavailability by applying a liquid assistant grinding technique. Nicotinic acid as a potential coformer for cocrystal preparation was predicted using a novel approach of the Hansen Solubility Parameter (HSP) group contribution method. Various evaluation parameters pertaining to confirm cocrystal formation, such as 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 effects of precipitation inhibitor Hydroxypropyl methyl cellulose (HPMC) on in-vivo bioavailability enhancement were also studied. MOD-NIC cocrystals formation was confirmed by integrating the results of instrumental techniques. Aqueous solubility and in-vivo pharmacokinetic study proved 5.96 and 1.88 times higher bioavailability, respectively, in the case of prepared cocrystals compared to MOD alone, whereas bioavailability further increased by 2.72 times when these cocrystals were administered in the 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.
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