In Silico Screening of Coformers, Design and Characterization of Novel Etodolac Co-crystals

Abstract

Co-crystallization offers an alternative that has enormous potential to provide new stable structures with improved pharmacokinetic properties of an Active Pharmaceutical Ingredient (API). Pharmaceutical co-crystals are multicomponent solid forms made up of neutral molecules of API and pharmaceutically acceptable coformers in a crystal lattice. Co-crystals are increasingly popular in pharmaceutical industry since they extend an opportunity to improve and tailor the physicochemical properties of a given API without affecting the intrinsic activity of the molecule. This is particularly important in case of BCS ClassII drugs having poor aqueous solubility and bioavailability. Etodolac,a BCS class II drug is taken as model drug. Here a very effective insilico screening method is developed for the virtual screening of coformers. Eight coformers from the GRAS list were screened. Binding affinity and possibility of Hydrogen bond interaction were determined computationally.The coformer which showed good binding score was selected for further study. Co-crystal was prepared by solvent assisted grinding. It was characterized by FTIR, DSC TGA, Powder XRD and SEM.Equilibrium solubility studies were also conducted. The prepared cocrystals showed remarkable improvement in aqueous solubility. The insilico screening method developed is a very useful computational tool for improving the efficiency of coformer screen by limiting the candidate coformers to be studied experimentally to only those compounds which show good binding score.