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.
Cite this paper
Xia, Y. , Jiang, C. and Zhang, J. (2021). Optimization of Carbamazepine-Succinic Acid Cocrystal Preparation Using Quality by Design Approach. Open Access Library Journal, 8, e7074. doi: http://dx.doi.org/10.4236/oalib.1107074.
Thakuria, R., Delori, A., Jones, W., Lipert, M.P., Roy, L. and Rodríguez-Hornedo, N. (2013) Pharmaceutical Cocrystals and Poorly Soluble Drugs. International Journal of Pharmaceutics, 453, 101-125. https://doi.org/10.1016/j.ijpharm.2012.10.043
Karagianni, A., Malamatari, M. and Kachrimanis, K. (2018) Pharmaceutical cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs. Pharmaceutics, 10, 18. https://doi.org/10.3390/pharmaceutics10010018
Duggirala, N.K., Perry, M.L., Almarsson, Ö. and Zaworotko, M.J. (2016) Pharmaceutical Cocrystals: Along the Path to Improved Medicines. Chemical Communications, 52, 640-655. https://doi.org/10.1039/C5CC08216A
Bolla, G. and Nangia, A. (2016) Pharmaceutical Cocrystals: Walking the Talk. Chemical Communications, 52, 8342-8360. https://doi.org/10.1039/C6CC02943D
Takata, N., Shiraki, K., Takano, R., Hayashi, Y. and Terada, K. (2008) Cocrystal Screening of Stanolone and Mestanolone Using Slurry Crystallization. Crystal Growth & Design, 8, 3032-3037. https://doi.org/10.1021/cg800156k
Kale, D.P., Zode, S.S. and Bansal, A.K. (2017) Challenges in Translational Development of Pharmaceutical Cocrystals. Journal of Pharmaceutical Sciences, 106, 457-470.
https://doi.org/10.1016/j.xphs.2016.10.021
Peltonen, L. (2018) Practical Guidelines for the Characterization and Quality Control of Pure Drug Nanoparticles and Nano-Cocrystals in the Pharmaceutical Industry. Advanced Drug Delivery Reviews, 131, 101-115.
https://doi.org/10.1016/j.addr.2018.06.009
Thakor, P., Yadav, B., Modhani, S. and Shastri, N.R. (2020) Preparation and Optimization of Nano-Sized Cocrystals Using Quality by Design Approach. CrystEngComm, 22, 2304-2314. https://doi.org/10.1039/C9CE01930H
Chabalenge, B., Korde, S., Kelly, A.L., Neagu, D. and Paradkar, A. (2020) Understanding Matrix Assisted Continuous Cocrystallisation Using Data Mining Approach in Quality by Design (QbD). Crystal Growth & Design, 20, 4540-4549.
https://doi.org/10.1021/acs.cgd.0c00338
