Solubility Prediction of Etodolac, Lamotrigine, Diazepam, and Clonazepamin in Cosolvent Mixtures Using UNIQUAC Model

Document Type : Research Article


1 Faculty of Chemical Engineering, University of Mohaghegh Ardabili, Ardabil, I.R. IRAN

2 Young Researchers and Elite Club, Shiraz Branch, Uslamic Azad University, Shiraz, I.R. IRAN

3 Nanotechnology Engineering, Sapienza University of Rome, Rome, ITALY

4 Research Institute of Petroleum Industry, Tehran, I.R. IRAN


Etodolac, Lamotrigine, diazepam, and clonazepamine are four important drugs in the pharmaceutical industry and optimizing the solvent concentration in the least amount can reduce the cost and toxicity of these drugs. Due to the lack of thermodynamic modeling based on the activity coefficient equation in previous studies for solubility of Etodolac, Lamotrigine, diazepam, and clonazepamine in aqueous solution, in this study, based on thermodynamic equations and UNIQUAC model, their solubility is optimized with the presence of water and ethanol. Based on the objective function defined, the error rate of the model optimization value was acceptable for each system. The results of this study can be used to better understand the intermolecular reaction of Etodolac, Lamotrigine diazepam, and clonazepamine in the presence of ethanol and water solvents. Also, the importance of the optimization results of this study in order to design a computer program to predict the solubility of these drugs is significant.


Main Subjects

[2] Pelblat A., Manzurola E., Abo Balal N., The Solubilities of Benzene Polycarboxylic Acids in Water, J. Chem. Thermodyn., 38: 565-571 (2006).
[3] Kong M.Z., Shi X.H., Cao Y.C., Zhou C.R., Solubility of Imidacloprid in Different Solvents, J. Chem. Eng. Data, 53: 615−618 (2008).
[5] Wang H., Wang Q., Xiong Z., Chen C., Shen B., Solubilities of benzoic Acid in Binary (benzyl alcohol+benzaldehyde) Solvent Mixtures, J. Chem. Thermodyn, 83: 61-66 (2015).
[6] Oliveira A.C., Coelho M.G., Pires R.F., Franco M.R., Solubility of Benzoic Acid in Mixed Solvents, J. Chem. Eng. Data, 52: 298-300 (2007).
[7] Mohd Abul K., Aws A., Musaed A., Ibrahim A.A., Raisuddin A., Nazrul H., Md Khalid A., Faiyaz Sh., Solubility Measurement and Various Solubility Parameters of Glipizide in Different Neat Solvents, ACS Omega, 5(3): 1708-1716 (2020).
[8] Xia Ch., Qianqian X., Zhiying L., Xianling Zh., Huilin Zh., Jia Zh., Rongrong L., Deman H., Solubility Determination, Model Correlation, and Solvent Effect Analysis of Nisoldipine in Different Solvent Systems at a Series of Temperature, Journal of Chemical & Engineering Data, 65(4): 1627-1635 (2020).
[9]  Alshehri S., Imam S.S., Hussain A., Altamimi M.A., Alruwaili N.K., Alotaibi F., Alanazi A., Shakeel F., Potential of Soliddispersions to Enhance Solubility, Bioavailability, and Therapeutic Efficacy of Poorly Water-Solubledrugs: Newer Formulation Techniques, Current Marketed Scenario and Patents, Drug Delivery, 27(1): 1625-1643(2020).
[11] Jacob S., Nair A.B., Shah J., Emerging Role of Nanosuspensions in Drug Delivery Systems, Biomater Res., 24(3):     (2020).
[12] Senjoti F.G., Timmins P., Conway B.R., Smith A.M., Optimizing Ophthalmic Delivery of a Poorly Water Soluble Drug from an Aqueous In Situ Gelling System, European Journal of Pharmaceutics and Biopharmaceutics (2020).
[14] Anderson T.F., Prausnitz J.M., Application of the UNIQUAC Equation to Calculation of Multicomponent Phase Equilibriums. 2. Liquid-Liquid Equilibriums, Industrial & Engineering Chemistry Process Design and Development, 17(4): 561-567 (1978).
[15] Prausnitz J.M., Lichtenthaler R.N., de Azevedo E.G., “Molecular Thermodynamics of Fluid-Phase Equilibria” (3rd ed.), Prentice Hall PTR; New Jersey (1999).
[16] Thomsen K., Rasmussen P., Modeling of Vapor–Liquid–Solid Equilibrium in Gas–Aqueous Electrolyte Systems, Chem. Eng. Sci., 54: 1787–1802 (1999).
[17] Jaime W.M., Hector R.G., Felipe H.L., Raquel R.R., Activity Coefficients of NaClO4 in (PEG 4000 + H2O) Mixtures at (288.15, 298.15 and 308.15) K. Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 39(2): 145-157 (2020).
[19] Shayanfar A., Fakhree M.A.A., Acree W.E., Jouyban A., Solubility of Lamotrigine, Diazepam, and Clonazepam in Ethanol+Water Mixtures at 298.15 K, J. Chem. Eng. Data, 54: 1107−1109 (2009).
[21] Matsuda H., Kaburagi K., Matsumoto S., Kurihara K., Tochigi K., Tomono K., Prediction of Solubilities of Pharmaceutical Compounds in Water + Co-Solvent Systems Using an Activity Coefficient Model, Chem. Eng. Data., 54: 480 (2009).
[22] Shuai Yu., Wenguo X., Fumin X., Yan Ch., Bing L., Solubility and Thermodynamic Properties of Nimodipine in Pure and Binary Solvents at a Series of Temperatures, The Journal of Chemical Thermodynamics,152: 106259 (2020).
[23] Delgado D., Bahamón-Hernandez O., Cerquera N., Ortiz C., Martínez F., Rahimpour E., Jouyban A., Acree W., Solubility of Sulfadiazine in (Acetonitrile + Methanol) Mixtures: Determination, Correlation, Dissolution Thermodynamics and Preferential Solvation, Journal of Molecular Liquids, 322: 114979 (2021).
[24] Jafari P., Rahimpour E., Acee W.E., Jouyban A., Prediction of Drug Solubility in Ethylene Glycol + Water Mixtures Using Generally Trained Cosolvency Models, Journal of Molecular Liquids, 328: 115325 (2021).
[25] Wei J., Chen Sh., Fu H.L., Wang X., Li H., Lin J., Xu F., He Ch., Liang X., Tang H., Shu G., Zhang W., Measurement and Correlation of Solubility Data for Atorvastatin Calcium in Pure and Binary Solvent Systems from 293.15 K to 328.15 K, Journal of Molecular Liquids, 324: 115124 (2021).
[26] Borra A., Kosuru R.K., Bharadwaj R., Satyavathi B., Measurement and Modeling of Solubility of Furan 2-Carboxylic Acid in Mono and Binary Systems, Journal of Molecular Liquids, 326: 115271 (2021)
[27] Agrawal N., Rangaiah G., Ray A.K., Gupta S.K., Multi-Objective Optimization of the Operation of an Industrial Low-Density Polyethylene Tubular Reactor Using Genetic Algorithm and Its Jumping Gene Adaptations, Industrial and Engineering Chemistry Research, 45(9): 3182 -3199 (2006).
[28] Cao K., Feng X., Ma H., Pinch Multi-Agent Genetic Algorithm for Optimizing Water-Using Networks, Computers and Chemical Engineering, 31(12): 1565- 1575 (2007).
[29]Elliott L., Ingham D., Kyne A., Mera N., Pourkashanian M., Wilson C., A Novel Approach to Mechanism Reduction Optimization for an Aviation Fuel/Air Reaction Mechanism Using a Genetic Algorithm, Journal of Engineering for Gas Turbines and Power, 128(2): 255- 263 (2006).
[30] Jezowski J., Bochenek R., Poplewski G., On Application of Stochastic Optimization Techniques to Designing Heat Exchanger- and Water Networks, Chemical Engineering and Processing: Process Intensi cation, 46(11):1160- 1174 (2007).
[31] Hashemi S.H, Mousavi Dehghani S.A., Khodadadi H., Dinmohammad M., Hosseini S.M, Hashemi S.H., Optimization of Extended UNIQUAC Parameter for Activity Coefficients of Ions of an Electrolyte System Using Genetic Algorithms, Korean Chemical Engineering Research, 55(5): 652-659 (2017).
[32] Naito Y., Matsuda  H., Shimomura K., Kurihara K., Tochigi K., Tomono K., Measurement and Correlation of Solubilities of the Poorly Water-Soluble Pharmaceutical Compound Etodolac by Addition of Co-Solvents, Fluid Phase Equilibria, 357(2): 43-49 (2013).