Preparation, characterization and solubility study of tadalafil cocrystals

Abstract

Most of drugs and drug like components have low solubility in aqueous media, which directly influence drug efficacy. Many approaches have been developed to improve drug solubility. Recently, crystal engineering as a novel method was applied to adjust drug physicochemical properties such as solubility. Cocrystals are crystalline materials composed of two or more different molecules, typically active pharmaceutical ingredient (API) and co-crystal formers (coformers) which constitute non-covalent bonds. In this study, tadalafil-methylparaben cocrystal was prepared and the thermodynamic solubility was evaluated in phosphate buffer solution and in presence of polymer and surfactant. Aim: Aim of this study was preparation and characterization of tadalafil-methylparaben cocrystal and evaluation of aqueous solubility and solution stability in presence of surfactant and polymer. Methods: Cocrystal formation between tadalafil and methylparaben was performed by solvent drop grinding based on the reported method in the literature. Prepared cocrystal was characterized by differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD). Then, the solubility and solution stability of cocrystal at different conditions were determined in phosphate buffer solution and in presence of sodium lauryl sulfate (SLS) and poly vinyl pyrrolidone (PVP). Results: Solubility studies of cocrystal in phosphate buffer showed improvement in comparison to Tadalafil. Tadalafil–methylparaben cocrystal instability in solution was enhanced by adding SLS and PVP however they could not have significant effect on cocrystal solubility compared to tadalafil.

Conclusion: Cocrystal formation of tadalafil with methylparaben has the ability to change solution stability in presence of PVP and SLS. Overall, this method could be used to alter physicochemical properties of non-ionizable drugs such as tadalafil.