Preferential Solvation of Fenofibrate in (Ethanol or Acetone) + Water Mixtures at 298.15 K

Document Type : Research Note


1 Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664, I.R. IRAN+/Kimia Idea Pardaz Azarbayjan (KIPA) Science Based Company, Tabriz University of Medical Science, , Tabriz, I.R. IRAN

2 Grupo de Investigaciones Farmacéutico-Fisicoquímicas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia –Sede Bogotá, Cra. 30 No. 45-03, Bogotá D.C., COLOMBIA

3 Department of Chemistry, University of North Texas, Denton, TX 76203-5070, USA


The aim of this communication was to expand the results of numerical analyses performed by Sun et al. on their experimental solubility of fenofibrate in aqueous mixtures of ethanol and acetone at 298.15 K, in terms of the evaluation of the preferential solvation of this compound by the organic solvents and water in the saturated mixtures based on the inverse Kirkwood-Buff integrals (IKBI). According to the results, this drug is preferentially solvated by water in water-rich mixtures but preferentially solvated by the cosolvents in mixtures with intermediate composition and also in cosolvent-rich mixtures. Preferential solvation by water in water-rich mixtures may be due to hydrophobic hydration around non-polar moieties of this drug. Moreover, it is conjecturable that in regions with preferential solvation by the cosolvents the drug is acting as Lewis acid with the cosolvent molecules because they are more basic than water.


Main Subjects

[1] Wodlinger A.M., Cardiovascular Drugs, in: “Remington: The Science and Practice of Pharmacy”, 21st Ed., Gennaro A. R. (Editor), Lippincott Williams & Wilkins, Philadelphia (2005).
[2] “US Pharmacopeia”, 31st ed., United States Pharmacopeial Convention, Rockville, MD (2008).
[3] Yadav V.B., Yadav A.V., Enhancement of Solubility and Dissolution rate of Fenofibrate by Melt Granulation Technique, Int. J. PharmTech Res., 1: 256-263 (2009).
[4] Martin A., Bustamante P., Chun A.H.C., “Physical Chemical Principles in the Pharmaceutical Sciences”, 4th ed., Lea & Febiger, Philadelphia, PA (1993).
[5] Sun H., Liu B., Liu P., Zhang J., Wang Y., Solubility of Fenofibrate in Different Binary Solvents: Experimental Data and Results of Thermodynamic Modeling, J. Chem. Eng. Data, 61: 3177-3183 (2016).
[6] Yalkowsky S.H., Roseman T.J., Solubilization of Drugs by Cosolvents, in: “Techniques of Solubilization of Drugs”, Yalkowsky S. H. (editor), Marcel Dekker, Inc., New York, NY (1981).
[7] Rubino J.T., Cosolvents and Cosolvency, in: “Encyclopedia of Pharmaceutical Technology”, Swarbrick J., Boylan J. C. (Editors), Marcel Dekker, Inc., New York, NY (1988), vol. 3, p. 375-398.
[8] Jouyban A., “Handbook of Solubility Data for Pharmaceuticals”, CRC Press, Boca Raton, FL, (2010).
[9] Bustamante P., Romero S., Peña A., Escalera B., Reillo A., Nonlinear Enthalpy-Entropy Compensation for the Solubility of Drugs in Solvent Mixtures: Paracetamol, Acetanilide and Nalidixic Acid in Dioxane-Water, J. Pharm. Sci., 87: 1590-1596 (1998).
[10] Martínez F., Peña M.Á., Bustamante P., Thermodynamic Analysis and Enthalpy-Entropy Compensation for the Solubility of Indomethacin in Aqueous and Non-Aqueous Mixtures, Fluid Phase Equilib., 308: 98-106 (2011)
[11] Marcus Y., “Solvent Mixtures: Properties and Selective Solvation”, Marcel Dekker, Inc., New York, NY (2002).
[12] Marcus Y., On the Preferential Solvation of Drugs and PAHs in Binary Solvent Mixtures, J. Mol. Liq., 140: 61-67 (2008).
[13] Jiménez D. M., Cárdenas Z.J., Delgado D.R., Martínez F., Jouyban A., Preferential Solvation of Methocarbamol in Aqueous Binary Cosolvent Mixtures at 298.15 K, Phys. Chem. Liq., 52: 726-737 (2014).
[14] Marcus Y., “The Properties of Solvents”, John Wiley & Sons, Chichester (1998).
[15] Noda K., Ohashi M., Ishida K., Viscosity and Densities at 298.15 K for Mixtures of Methanol, Acetone and Water, J. Chem. Eng. Data, 27: 326-328 (1982).
[16] Fedors R. F., A Method for Estimating Both the Solubility Parameters and Molar Volumes of Liquids, Polym. Eng. Sci., 14: 147-154 (1974).
[18] Delgado D. R., Peña M. Á., Martínez F., Preferential Solvation of Some Sulfonamides in Propylene Glycol + Water Solvent Mixtures According to the IKBI and QLQC Methods, J. Solution Chem., 43: 360-374 (2014).
[19] Cárdenas Z.J., Jiménez D.M., Martínez, F., Preferential Solvation of Ketoprofen in Some co-Solvent Binary Mixtures, J. Solution Chem., 43: 1904-1915 (2014).
[20] Jiménez D.M., Cárdenas Z.J., Delgado D.R., Peña M.Á., Martínez, F., Preferential Solvation of the Antioxidant Agent Daidzein in Some Aqueous co-Solvent Mixtures According to IKBI and QLQC Methods, J. Appl. Sol. Chem. Mod., 4: 110-118 (2015).
[21] Peña M.Á., Delgado D.R., Martínez F., Preferential Solvation of Some n-Alkyl p-Substituted-Benzoates in Propylene Glycol + Water co-Solvent Mixtures, Phys. Chem. Liq., 53: 455-466 (2015).