Abstract—Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and co-crystal former (CCF) of fumaric acid (FUM) and succinic acid (SA) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method for CBZ-FUM system and in all methods for CBZ-SA system. The findings from this analysis revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvents systems. DSC analysis had shown that the melting point of CBZ-FUM and CBZ-SA co-crystals were in the range similar to the previous study. The characterization using FT-IR indicated that the functional groups which include amides and carboxylic acids were presented in the co-crystal produced. Further study on the co-crystal solubility and dissolution rate is needed in order to access the efficacy of the co-crystal since the screening methods have been successfully confirmed the formation of the co-crystal.
Index Terms—Carbamazepine, co-crystal, stoichiometry, non-stoichiometry.
F. Ab Rahman, S. Abd Rahim, C. C. Tan, L. S. Han, and N. A. Ramlee are with the Faculty of Chemical & Natural Resources Engineering, fatinahabrahman@gmail.com, syarifah@ump.edu.my, choang_911@hotmail.com, cons819@hotmail.com, ashilaramle@gmail.com)
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Cite: Fatinah Ab Rahman, Syarifah Abd Rahim, Chou C. Tan, Souk H. Low, and Noor Ashila Ramle, "Carbamazepine-Fumaric Acid and Carbamazepine-Succinic Acid Co-crystal Screening Using Solution Based Method," International Journal of Chemical Engineering and Applications vol. 8, no. 2, pp. 136-140, 2017.
