Preparation and evaluation of pharmaceutical co-crystals for solubility enhancement of atorvastatin calcium

Abstract

Co-crystallization is one of the methods to enhance the solubility of hydrophobic drugs that belong to BCS class II. Preparation and characterization of atorvastatin calcium co-crystals by liquid-assisted grinding method using citric acid and nicotinamide as co-formers for solubility enhancement were the objective of the current research. All the prepared formulations were characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), zeta size analysis, dissolution and solubility studies. Solubility studies were performed in distilled water, pH 1.2 and pH 6.8. PXRD revealed the structural nature of the co-crystals formulations. FTIR, TGA and DSC confirmed the complex formation and have better thermal stability than individual components. SEM images exhibited the prism-like crystals with irregular and rough surfaces. Zeta size analysis showed the small particle size having large surface area that facilitates to improve the solubility. Dissolution and solubility studies of the formulations confirmed that solubility enhanced several folds in all media as compared to the solubility of available market drug. From all these studies, it can be concluded that co-crystallization technique enhanced the solubility of atorvastatin calcium by using liquid-assisted grinding method.