Optimization of Carbamazepine-Succinic Acid Cocrystal Preparation Using Quality by Design Approach

Abstract

The present investigation was aimed at using quality by design approach optimization of cocrystal preparation. The challenge was too many factors affect the final purity and yield. Carbamazepine (CBZ)-succinic acid (SA) was selected as a model cocrystal for this study. A Design of Experiments (DoE) approach, specifically Central Composite Design (CCD) with the aid of Response Surface Methodology (RSM) was used to optimize formulation variables for the synthesis of carbamazepine and succinic acid cocrystals using slurry crystallization. Design was applied for studying the effect of four independent variables (time, molar ratio, temperature, and concentration) on the yield. The experimental outcome indicated that the molar ratio significantly affects the yield of the cocrystal. Further, the optimized formulation was characterized by powder X-ray diffraction. It can be found that within a certain range, all obtained are pure cocrystal.