Employing supramolecular chemistry to improve biopharmaceutical parameters of selected NSAIDs

Abstract

Supramolecular chemistry is one of the prolific and escalating domains in pharmaceutical sciences and has proved to be a potential solution to the solubility of limited bioavailability problems of diacerein, oxaprozin, and etodolac. Three cocrystals of Diacerein with isonicotinamide, nicotinamide, and theophylline, three cocrystals of oxaprozin with citrulline, methionine, and asparagine, three eutectics of etodolac with syringic acid, ascorbic acid and nicotinic acid were prepared through the mechanochemical solvent drop-grinding method using ethanol as a solvent. The coformers were selected on the basis of CSD search and further, the characterization of these cocrystals was performed by various sophisticated analytical techniques such as DSC, FTIR, PXRD, and ssNMR. The structure determination of cocrystal of oxaprozin and diacerein was done via the information stored in the PXRD pattern. The crystal structure revealed new heteromeric linkage in the cocrystals which were dominant over the homomeric linkage among the drug molecules. In the presence of an eutectic system, phase diagram analysis was performed in the case of etodolac. In each binary mixture of etodolac with conformers, the plot of solidus and liquidus points against different mole fractions revealed the V shaped graph confirming the formation of eutectic. The prepared cocrystals and eutectics were then evaluated for improvements in solubility and dissolution parameters. All the cocrystals showed increased solubility and intrinsic dissolution rates. These studies were followed by pharmacokinetic studies which indicated an increase in the relative bioavailability of all the cocrystals and eutectics. The current study opens avenues for drug development through crystallization involving supramolecular chemistry techniques newline