Journal of Solution Chemistry

, Volume 40, Issue 7, pp 1279–1290 | Cite as

Partition Coefficients and Solubilities of Compounds in the Water–Ethanol Solvent System

  • Michael H. Abraham
  • William E. AcreeJr.


A new method for the prediction of solubility in the water–ethanol system has been devised. The method is based on the construction of equations for the prediction of partition coefficients from water to water–ethanol mixtures, based on the Abraham descriptors for compounds. Once partition coefficients have been predicted for a particular compound, only an experimental value for the solubility in ethanol is required for the prediction of solubilities in water–ethanol mixtures. Results of predictions are comparable to the Jouyban-Acree model that requires experimental solubilities in both water and ethanol.


Water–ethanol Solubility Partition coefficients Abraham descriptors Linear free energy relationship Multiple linear regression 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Supplementary material


  1. 1.
    Yalkowsky, S., Flynn, G., Amidon, G.: Solubility of nonelectrolytes in polar solvents. J. Pharm. Sci. 61, 983–984 (1972) CrossRefGoogle Scholar
  2. 2.
    Yalkowsky, S., Valvani, S., Amidon, G.: Solubility of nonelectrolytes in polar solvents. IV. Nonpolar drugs in mixed solvents. J. Pharm. Sci. 65, 1488–1493 (1976) CrossRefGoogle Scholar
  3. 3.
    Li, A., Yalkowsky, S.H.: Solubility of organic solutes in ethanol/water mixtures. J. Pharm. Sci. 83, 1735–1740 (1994) CrossRefGoogle Scholar
  4. 4.
    Millard, J.W., Alvarez-Nunez, F.A., Yalkowsky, S.H.: Solubilization by cosolvents. Establishing useful constants for the log-linear model. Int. J. Pharm. 245, 153–166 (2002) CrossRefGoogle Scholar
  5. 5.
    Machatha, S.G., Yalkowsky, S.H.: Bilinear model for the prediction of drug solubility in ethanol/water mixtures. J. Pharm. Sci. 94, 2731–2734 (2005) CrossRefGoogle Scholar
  6. 6.
    Acree, W.E. Jr., Zvaigzne, A.I.: Thermodynamic properties of nonelectrolyte solutions. Part 4. Estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the nearly ideal binary solvent (NIBS) and modified Wilson equations. Thermochim. Acta 178, 151–161 (1991) CrossRefGoogle Scholar
  7. 7.
    Matsuda, H., Kaburagi, K., Matsumoto, S., Kurihara, K., Tochigi, K., Tomono, K.: Solubilities of salicylic acid in pure solvents and binary mixtures containing cosolvent. J. Chem. Eng. Data 54, 480–484 (2009) Google Scholar
  8. 8.
    Pena, M.A., Reillo, A., Escalera, B., Bustamante, P.: Solubility parameter of drugs for predicting the solubility profile type of drugs within a wide range in solvent mixtures. Pharm. Nanotech. 321, 155–161 (2006) Google Scholar
  9. 9.
    Acree, W.E. Jr.: Mathematical representation of thermodynamic properties. Part 2. Derivation of the combined nearly ideal binary solvent (NIBS)/Redlich-Kister mathematical representation from a two-body and three-body interactional mixing model. Thermochim. Acta 198, 71–79 (1992) CrossRefGoogle Scholar
  10. 10.
    Abraham, M.H.: Scales of hydrogen bonding: their construction and application to physicochemical and biochemical processes. Chem. Soc. Rev. 22, 73–83 (1993) CrossRefGoogle Scholar
  11. 11.
    Abraham, M.H., Ibrahim, A., Zissimos, A.M.: The determination of sets of solute descriptors from chromatographic measurements. J. Chromatogr. A 1037, 29–47 (2004) CrossRefGoogle Scholar
  12. 12.
    Jouyban, A., Soltanpour, Sh., Soltani, S., Tamizi, E., Fakhree, M.A.A., Acree, W.E. Jr.: Prediction of drug solubility in mixed solvents using computed Abraham parameters. J. Mol. Liq. 146, 82–88 (2009) CrossRefGoogle Scholar
  13. 13.
    Fakhtree, M.A.A., Shayanfar, A., Acree, W.E.Jr., Jouyban, A.: Solubility of phenanthrene in binary mixtures of C1–C4 alcohols + 2-propanol and ethanol + methanol at 298.2 K. J. Chem. Eng. Data 54, 1405–1408 (2009) CrossRefGoogle Scholar
  14. 14.
    Abraham, M.H., Acree, W.E. Jr., Cometto-Muñiz, J.E.: Partition of compounds from water and air into amides. New J. Chem. 33, 2034–2043 (2009) (2009) CrossRefGoogle Scholar
  15. 15.
    Flanagan, K.B., Hoover, K.C., Garza, O., Hizon, A., Soto, T., Villegas, N., Acree, W.E. Jr., Abraham, M.H.: Mathematical correlation of 1-chloroanthraquinone solubilities in organic solvents with the Abraham solubility parameter model. Phys. Chem. Liq. 44, 377–386 (2006) CrossRefGoogle Scholar
  16. 16.
    Blake-Taylor, B.H., Delean, V.H., Acree, W.E. Jr., Abraham, M.H.: Mathematical correlation of salicylamide solubilities in organic solvents with the Abraham solvation parameter model. Phys. Chem. Liq. 45, 389–398 (2007) CrossRefGoogle Scholar
  17. 17.
    Abraham, M.H., Smith, R.E., Luchtefeld, R., Boorem, A.J., Luo, R., Acree, W.E. Jr.: Prediction of solubility of drugs and other compounds in organic solvents. J. Pharm. Sci. 99, 1500–1515 (2010) Google Scholar
  18. 18.
    Yamamoto, H., Ichikawa, K., Tokunaga, J.: Solubility of helium in methanol + water, ethanol + water, 1-propanol + water and 2-propanol + water solutions at 25 °C. J. Chem. Eng. Data 39, 155–157 (1994) CrossRefGoogle Scholar
  19. 19.
    Abraham, M.H., Grellier, P.L., McGill, R.A.: A quantitative measure of solvent solvophobic effect. J. Chem. Soc. Perkin Trans. II 339–345 (1988) Google Scholar
  20. 20.
    Young, C.L.: Hydrogen and Deuterium. Solubility Data Series, vol. 5/6. Pergamon Press, Oxford (1981) Google Scholar
  21. 21.
    Tokunaga, J.: Solubilities of oxygen, nitrogen and carbon dioxide in aqueous alcohol solutions. J. Chem. Eng. Data 20, 41–46 (1975) CrossRefGoogle Scholar
  22. 22.
    Winstein, S., Fainberg, A.H.: Correlation of solvolysis rates. IV. Solvent effects on enthalpy and entropy of activation for solvolysis of tert-butyl chloride. J. Am. Chem. Soc. 79, 5937–5950 (1957) CrossRefGoogle Scholar
  23. 23.
    Starobinets, G.L., Rakhman’ko, E.M., Leshchev, S.M.: Medium effects on the partition of organic non-electrolytes between mixed water–ethanol media and octane. Russ. J. Phys. Chem. 52, 2284–2287 (1978) Google Scholar
  24. 24.
    Seidell, A.: Solubilities of Organic Compounds, 3rd edn., vol. II. Van Nostrand, New York (1941) Google Scholar
  25. 25.
    Zhou, B., Cai, W., Zou, L.: Thermodynamic functions for transfer of anthracene from water to (water + alcohol) mixtures at 298.15 K. J. Chem. Eng. Data 48, 742–745 (2003) CrossRefGoogle Scholar
  26. 26.
    Abraham, M.H.: Unpublished work on the solubility of benzyl chloride (2010) Google Scholar
  27. 27.
    Li, A., Andren, A.A.: Solubility of polychlorinated biphenyls in water/alcohol mixtures. 1. Experimental data. Environ. Sci. Technol. 28, 47–52 (1994) CrossRefGoogle Scholar
  28. 28.
    Xiao, M., Yan, W., Zhang, Z.: Solubilities of apigenin in ethanol + water at different temperatures. J. Chem. Eng. Data 55, 3346–3348 (2010) CrossRefGoogle Scholar
  29. 29.
    Peng, B., Yan, W.: Solubility of luteolin in ethanol + water mixed solvents at different temperatures. J. Chem. Eng. Data 55, 583–585 (2010) CrossRefGoogle Scholar
  30. 30.
    Peng, B., Li, R., Yan, W.: Solubility of rutin in ethanol + water at (273.15 to 323.15) K. J. Chem. Eng. Data 54, 1378–1381 (2009) CrossRefGoogle Scholar
  31. 31.
    Bose, K., Kundu, K.K.: Thermodynamics of transfer of p-nitroaniline from water to alcohol–water mixtures at 25 °C and the structure of water in these mixtures. Can. J. Chem. 55, 3961–3965 (1977) CrossRefGoogle Scholar
  32. 32.
    Peña, M.A., Reillo, A., Escalera, B., Bustamente, P.: Solubility parameter of drugs for predicting the solubility profile type within a wide polarity range in solvent mixtures. Int. J. Pharm. 321, 155–161 (2006) CrossRefGoogle Scholar
  33. 33.
    Gantiva, M., Yurquina, A., Martinez, F.: Solution thermodynamics of ketoprofen in ethanol + water cosolvent mixtures. J. Chem. Eng. Data 55, 113–118 (2010) CrossRefGoogle Scholar
  34. 34.
    Perez-Camino, M., Sanchez, E., Balon, M., Maestre, A.: Thermodynamic functions for the transfer of 1-naphthoic acid from water to mixed aqueous solvents at 298 K. J. Chem. Soc. Faraday Trans. I 81, 1555–1561 (1985) CrossRefGoogle Scholar
  35. 35.
    Jouyban, A., Chan, H.K., Romero, S., Khoubnasabjafari, M., Bustamante, P.: Solubility prediction in water–ethanol mixtures based on the excess free energy approach using a minimum number of experimental data. Pharmazie 59, 117–120 (2004) Google Scholar
  36. 36.
    Lukavenko, O.N., Eltsov, S.V., Grigorovich, A.V., Mchedlov-Petrossyan, N.O.: Solubility and fluorescence lifetime of 2,5-diphenyloxazole and 1,4-bis(5-phenyloxazolyl-2)benzene in water–ethanol and water-acetone systems. J. Mol. Liq. 145, 167–172 (2009) CrossRefGoogle Scholar
  37. 37.
    Liu, Y., Wang, J., Wang, X., Liu, P., Pang, F.: Solubility of valsartan in different organic solvents and ethanol + water binary mixtures from (278.15 to 313.15 ) K. J. Chem. Eng. Data 54, 986–988 (2009) CrossRefGoogle Scholar
  38. 38.
    Zhao, G., Yan, W.: Experimental determination of solubilities of betulin in acetone + water and ethanol + water mixed solvents at T=(278.2,288.2,298.2,308.2, and 318.2) K. J. Chem. Eng. Data 52, 2365–2367 (2007) CrossRefGoogle Scholar
  39. 39.
    Breon, T.L., Paruta, A.N.: Solubility profiles for several barbiturates in hydroalcoholic mixtures. J. Pharm. Sci. 59, 1306–1313 (1970) CrossRefGoogle Scholar
  40. 40.
    Manzo, R.H., Ahumada, A.A., Luna, E.: Effects of medium on solubility III: hydrophilic-lipophilic character exhibited by some functional groups having oxygen or nitrogen in ethanol–water. J. Pharm. Sci. 73, 1094–1097 (1984) CrossRefGoogle Scholar
  41. 41.
    Manzo, R.H., Ahumada, A.A., Luna, E.: Effects of medium on solubility IV: comparison of the hydrophilic-lipophilic character exhibited by functional groups in ethanol–water. J. Pharm. Sci. 73, 1869–1871 (1984) CrossRefGoogle Scholar
  42. 42.
    Ali, H.S.M., York, P., Blagden, N., Soltanpour, S., Acree, W.E. Jr., Jouyban, A.: Solubility of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2 K. J. Chem. Eng. Data 55, 578–582 (2010) CrossRefGoogle Scholar
  43. 43.
    Desai, K.G.H., Kulkarni, A.R., Aminabhavi, T.M.: Solubility of rofecoxib in the presence of methanol, ethanol and sodium lauryl sulfate at (298.15, 301.15, and 308.15) K. J. Chem. Eng. Data 48, 942–945 (2003) CrossRefGoogle Scholar
  44. 44.
    Liu, C., Desai, K.G.H., Liu, C.: Solubility of valdecoxib in the presence of ethanol and sodium lauryl sulfate at (298.15, 303.15, and 308.15) K. J. Chem. Eng. Data 49, 1847–1850 (2004) CrossRefGoogle Scholar
  45. 45.
    Paruta, A.N.: Solubility profiles for antipyrine and aminopyrine in hydroalcoholic solutions. J. Pharm. Sci. 56, 1565–1569 (1967) CrossRefGoogle Scholar
  46. 46.
    Abraham, M.H., Acree, W.E. Jr.: Equations for the transfer of neutral molecules and ionic species from water to organic phases. J. Org. Chem. 75, 1006–1015 (2010) CrossRefGoogle Scholar
  47. 47.
    Franks, F.: The properties of aqueous solutions of non-electrolytes. In: Franks, F. (ed.) Physico-Chemical Processes in Mixed Aqueous Solvents. Heinemann, London (1967) Google Scholar
  48. 48.
    Sprunger, L.M., Achi, S.S., Pointer, R., Blake-Taylor, B.H., Acree, W.E. Jr., Abraham, M.H.: Development of Abraham model correlations for solvation characteristics of linear alcohols. Fluid Phase Equilib. 286, 170–174 (2009) CrossRefGoogle Scholar
  49. 49.
    Li, A., Pinsuwan, S., Yalkowsky, S.H.: Estimation of solubility of organic compounds in 1-octanol. Ind. Eng. Chem. 34, 915–920 (1995) CrossRefGoogle Scholar
  50. 50.
    Hilal, S.H., Karickhoff, S.W., Carreira, L.A.: Prediction of the solubility, activity coefficient and liquid/liquid partition coefficient of organic compounds. QSAR & Comb. Sci. 23, 709–720 (2004) CrossRefGoogle Scholar
  51. 51.
    Eckert, F.: Prediction of solubility with COSMO-RS. In: Letcher, T.M. (ed.) Developments and Applications in Solubility. Royal Society of Chemistry, Cambridge (2007) Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of ChemistryUniversity College LondonLondonUK
  2. 2.Department of ChemistryUniversity of North TexasDentonUSA

Personalised recommendations