Ethenzamide, a non-steroidal anti-inflammatory drug, is used to treat pain, inflammation, fever and rheumatism. However, it has low solubility and belongs to class II of the biopharmaceutical classification system. In order to improve the solubility of ethenzamide, the cocrystal of ethenzamide was prepared and characterized according to the synthesis principle of hydrogen bond supramolecular synthons in crystal engineering. The ETZ·2TMA·MeOH cocrystal was obtained by the solution evaporation crystallization method. The cocrystal structure was characterized by Single Crystal X-ray Diffractometer. The single crystal belongs to orthorhombic crystal system with space group P212121 (no.19), a = 12.9863 (9) Å, b = 16.6603 (11) Å, c = 25.9260 (16) Å, V = 5609.2 (6) Å3, Z = 8, T = 170.00 K. The main forces are the formation of intermolecular hydrogen bonds between the amide groups on ethenzamide and the carboxyl groups on trimesic acid and the hydroxyl group on methanol. In addition, the solubility of ethenzamide and ETZ·2TMA·MeOH cocrystal was determined. The results show that, in contrast to most cocrystal systems that improve solubility, the solubility of ETZ·2TMA·MeOH decreased to 19.30% of pure ethenzamide.
Cite this paper
Lin, S. , Zhang, J. , Sun, W. , Ren, P. , Jiang, J. and Jiang, C. (2023). New Ethenzamide-Trimesic Acid Cocrystal: Equilibrium Solubility. Open Access Library Journal, 10, e247. doi: http://dx.doi.org/10.4236/oalib.1110247.
Ozawa, M., Hasegawa, K., Yonezawa, Y. and Sunada, H. (2002) Preparation of Solid Dispersion for Ethenzamide-Carbopol and Theophylline-Carbopol Systems Using a Twin Screw Extruder. Chemical and Pharmaceutical Bulletin, 50, 802-807.
https://doi.org/10.1248/cpb.50.802
Aitipamula, S., Chow, P.S. and Tan, R.B.H. (2010) Conformational and Enantiotropic Polymorphism of a 1:1 Cocrystal Involving Ethenzamide and Ethylmalonic Acid. CrystEngComm, 12, 3691-3697.
https://doi.org/10.1039/c004491a
Nechipadappu, S.K. and Trivedi, D.R. (2018) Cocrystal of Nutraceutical Sinapic Acid with Active Pharmaceutical Ingredients Ethenzamide and 2-Chloro-4-Nitrobenzoic Acid: Equilibrium Solubility and Stability Study. Journal of Molecular Structure, 1171, 898-905. https://doi.org/10.1016/j.molstruc.2018.06.074
Khatioda, R., Saikia, B., Das, P.J. and Sarma, B. (2017) Solubility and in Vitro Drug Permeation Behavior of Ethenzamide Cocrystals Regulated in Physiological PH Environments. CrystEngComm, 19, 6992-7000. https://doi.org/10.1039/C7CE01626C
Aitipamula, S., Chow, P.S. and Tan, R.B.H. (2010) Polymorphs and Solvates of a Cocrystal Involving an Analgesic Drug, Ethenzamide, and 3, 5-Dinitrobenzoic Acid. Crystal growth & design, 10, 2229-2238. https://doi.org/10.1021/cg9015178
Khatioda, R., Bora, P. and Sarma, B. (2018) Trimorphic Ethenzamide Cocrystal: In Vitro Solubility and Membrane Efflux Studies. Crystal Growth & Design, 18, 4637-4645. https://doi.org/10.1021/acs.cgd.8b00603
Hariprasad, V.M., Nechipadappu, S.K. and Trivedi, D.R. (2016) Cocrystals of Ethenzamide: Study of Structural and Physicochemical Properties. Crystal Growth & Design, 16, 4473-4481. https://doi.org/10.1021/acs.cgd.6b00606
Kozak, A., Marek, P.H. and Pindelska, E. (2019) Structural Characterization and Pharmaceutical Properties of Three Novel Cocrystals of Ethenzamide with Aliphatic Dicarboxylic Acids. Journal of pharmaceutical sciences, 108, 1476-1485.
https://doi.org/10.1016/j.xphs.2018.10.060
Nechipadappu, S.K., Tekuri, V. and Trivedi, D.R. (2017) Pharmaceutical Co-Crystal of Flufenamic Acid: Synthesis and Characterization of Two Novel Drug-Drug Co-Crystal. Journal of Pharmaceutical Sciences, 106, 1384-1390.
https://doi.org/10.1016/j.xphs.2017.01.033
Sarmah, K.K., Boro, K., Arhangelskis, M. and Thakuriaet, R. (2017) Crystal Structure Landscape of Ethenzamide: A Physicochemical Property Study. CrystEngComm, 19, 826-833. https://doi.org/10.1039/C6CE02057G
Aitipamula, S., Chow, P.S. and Tan, R.B.H. (2009) Dimorphs of a 1:1 Cocrystal of Ethenzamide and Saccharin: Solid-State Grinding Methods Result in Metastable Polymorph. CrystEngComm, 11, 889-895. https://doi.org/10.1039/b821373a
