Preparation of cocrystals to improve physicochemical properties of drugs

Abstract

Solubility is a crucial physicochemical property of pharmaceutical compounds in different stages of drug discovery and development. Cocrystal formation is one of the methods to improve solubility of drugs. They are composed of two compounds via noncovalent interactions predominantly hydrogen bonding in certain stoichiometric ratio. Cocrystals may be prepared in a metastable crystal form or an amorphous form, which are named amorphous cocrystal or coamorphous. The aims of this study are 1) preparation of different pharmaceutical cocrystals of poorly soluble drug 2) characterization of the cocrystals using different instrumental analysis methods and 3) investigation of the physicochemical properties i.e. solubility and dissolution rate of the pharmaceutical cocrystals.Methods A number of low soluble drugs from class II biopharmaceutical classification system (BCS) i.e. carbamazepine, atorvastatin calcium, carvedilol, glibenclamide and ketoconazole with three pharmaceutical coformers (nicotinamide, cinnamic acid and para-amino benzoic acid) were selected and their cocrystals (drug-drug or drug-coformer cocrystals) were prepared by solvent evaporation approach. The prepared pharmaceutical cocrystals or coamorphous were characteristized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and Fourier transform infrared spectroscopy (FT-IR) methods then their physicochemical properties including the solubility, dissolution rate and the solution stability were investigated. Results The results of different instrumental analysis methods confirm the cocrystal or coamorphous formation between drug-drug or drug-coformers. Solubility and dissolution rate of cocrystal or coamorphous were improved in compare with those of non-process drugs. Solution stability and solubility of coformer are significant factors in improving the solubility. In addition amorphous cocrystals give higher solubility than pure amorphous drugs. Conclusion In conclusion, a cocrystal is a crucial approach for improving physicochemical properties such as solubility and dissolution rate of drugs. The both solubility and stability of coformer had played main roles in solubility of cocrystal. The coamorphous systems were shown to have improved solution stability as compared to amorphous forms of drugs.