Solubility and dissolution rate of a carbamazepine-cinnamic acid cocrystal

Abstract

Synthesis of cocrystals is one of the methods to alter physicochemical properties of drugs. A cocrystal of carbamazepine (CBZ) and cinnamic acid (CIN) was synthesized using solvent evaporation and was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). The kinetic solubility, powder dissolution rate and stability of CBZ in aqueous solution were compared with those of cocrystal form (CBZ-CIN). Quantification of CBZ was evaluated using a UV-spectrophotometric technique in the presence of CIN that their spectrums are highly overlapped. Therefore, a recently developed net analyte signal standard addition method (NASSAM) was applied for determination of CBZ in the presence of CIN. The PXRD, DSC and FT-IR studies confirm that the cocrystal formation between CBZ and CIN and the developed NASSAM method can be used to quantitative determination of CBZ concentration in presence of CIN. The powder dissolution rate of cocrystal of CBZ-CIN is higher than CBZ and the kinetic solubility study show that the cocrystal is stable in dissolution medium and the aqueous solubility of CBZ-CIN is higher than CBZ. These findings show that formation of CBZ-CIN cocrystal is a suitable method to increase dissolution rate and solubility of CBZ and NASSAM is a valuable analytical method to quantitative determination of drugs in the presence of coformer in cocrystal studies. (C) 2013 Elsevier B.V. All rights reserved.