Preparation and Characterization of Theophylline−Nicotinamide Cocrystal

Abstract

Cocrystals have been increasingly recognized as an attractive alternative for solid forms of drug products. In this work, nicotinamide (NCT) was employed as a cocrystal former with the active pharmaceutical ingredient theophylline (TP). The theophylline−nicotinamide cocrystal (hereafter TP-NCT cocrystal) was prepared by solid-state grinding and slow evaporation from ethanol, and was characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage optical microscopy (HSM), Raman spectroscopy, and powder X-ray diffraction (PXRD) techniques. Pharmaceutically relevant properties such as powder dissolution rate, solubility and dynamic vapour sorption (DVS) of the TP-NCT cocrystal were evaluated. The results show that, the TP-NCT cocrystal, obtained in a 1:1 molar ratio of theophylline and nicotinamide, possesses unique thermal, spectroscopic, and X-ray diffraction properties. In addition, the solubility and hygroscopicity of the TP-NCT cocrystal were considerably higher than those of anhydrous theophylline.