Thermodynamic Study of the Solubility of Naproxen in Some 2-Propanol + Water Mixtures

  • Diego Iván Caviedes Rubio Universidad Cooperativa de Colombia
  • Gerson Andrés Rodríguez Rodríguez Universidad Cooperativa de Colombia
  • Daniel Ricardo Delgado Universidad Cooperativa de Colombia


The equilibrium solubilities of the anti-inflammatory drug naproxen (NPX) in 2-propanol + water mixtures were determined at several temperatures from 298.15 to 313.15 K. The Gibbs energy, enthalpy, and entropy of solution and of mixing were obtained from these solubility data. The solubility was maximal in φ1 = 0.90 and very low in pure water at all the temperatures studied. A non-linear plot of ∆solnH° vs. ∆solnG° with negative slope from pure water up to 0.20 in volume fraction of 2-propanol and positive beyond this composition up pure 2-propanol was obtained at the mean temperature, 305.55 K. Accordingly, the driving mechanism for NPX solubility in the water-rich mixtures was the entropy, probably due to water-structure loss around non-polar moieties of the drug and for the 2-propanol-rich mixtures it was the enthalpy, probably due to its better solvation of the drug.


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Referencias Bibliográficas

Bevington P. 1969. Data Reduction and Error Analysis for the Physical Sciences. McGraw-Hill Book. New York, 103p.

Bustamante P, Romero S, Peña A, Escalera B y Reillo A. 1998. Enthalpy−entropy compensation for the solubility of drugs in solvent mixtures: paracetamol, acetanilide, and nalidixic acid in dioxane-water. Journal of Pharmaceutical Sciences. 87:1590-1596.

Delgado DR y Martinez F. 2013. Solution thermodynamics of sulfadiazine in ethanol + water mixtures. Journal of Molecular Liquids, 187: 99-105.

Delgado DR, Holguín AR, Almanza OA, Martínez F y Marcus Y. 2011b. Solubility and preferential solvation of meloxicam in ethanol + water mixtures. Fluid Phase Equilibria, 305: 88-95.

Delgado DR, Rodríguez GA y Martínez F. 2013a. Thermodynamic study of the solubility of sulfapyridine in some ethanol + water mixtures. Journal of Molecular Liquids, 177: 156-161.

Delgado DR, Rodríguez GA, Holguín AR, Martínez F y Jouyban A. 2013b. Solubility of sulfapyridine in propylene glycol + water mixtures and correlation with the Jouyban-Acree model. Fluid Phase Equilibria, 341: 86-95.

Delgado DR, Romdhani A y Martínez F. 2012. Solubility of sulfamethizole in some propylene glycol + water mixtures at several temperatures. Fluid Phase Equilibria, 322-323: 113-119.

Delgado DR, Romdhani A. y Martínez F. 2011a. Thermodynamics of sulfanilamide solubility in propylene glycol + water mixtures. Latin American Journal of Pharmacy 30: 2024-2030.

Delgado DR, Ruidiaz MA, Gómez SM, Gantiva M y Martínez F. 2010. Thermodynamic study of the solubility of sodium naproxen in some ethanol + water mixtures. Química Nova, 33: 1923-1927.

Holguín AR, Delgado DR y Martínez F. 2012. Thermodynamic study of the solubility of triclocarban in ethanol + propylene glycol mixtures. Química Nova, 35: 280-285.

Jiménez DM, Cardenas ZJ, Delgado DR, Peña MA y Matínez F. 2015. Solubility temperature dependence and preferential solvation of sulfadiazine in 1,4-dioxane + water co-solvent mixtures. Fluid Phase Equilibria, 397: 26-36

Jouyban A. 2010. Handbook of Solubility Data for Pharmaceuticals, CRC Press, Boca Raton, FL, 405p.

Krug RR, Hunter WG y Grieger R.A. 1976a. Enthalpy-entropy compensation. 1. Some fundamental statistical problems associated with the analysis of van't Hoff and Arrhenius data. The Journal of Physical Chemistry, 80: 2335–2341.

Krug RR, Hunter WG y Grieger RA. 1976a. Enthalpy-entropy compensation. 2. Separation of the chemical from the statistical effect. The Journal of Physical Chemistry, 80: 2341–2351

Marcus Y. 1998. The Properties of Solvents, John Wiley & Sons, Chichester, 103p.

Meloun M. y Ferencíková Z. 2012. Enthalpy–entropy compensation for some drugs dissociation in aqueous solutions. Fluid Phase Equilibria, 328: 31-41

Mishra B. Sahoo J. y Kumar P. 2015. Formulation and process optimization of naproxen nanosuspensions stabilized by hydroxy propyl methyl cellulose. Carbohydrate Polymers, 127: 300-308.

Mohammadzade M, Barzegar-Jalali M y Jouyban A. 2015. Solubility of naproxen in 2-propanol + water mixtures at various temperatures. Journal of Molecular Liquids, 206: 110-113.

Perlovich GL, Kurkov SV, Kinchin AN y Bauer-Brandl A. 2004. Thermodynamics of solutions III: Comparison of the solvation of (+)-naproxen with other NSAIDs. European Journal of Pharmaceutics and Biopharmaceutics, 57: 411-420.

Perlovich GL, Strakhova NN, Kazachenko VP, Volkova TV, Tkachev VV, Schaper, KJ y Raevsky OA. 2008. Sulfonamides as a subject to study molecular interactions in crystals and solutions: Sublimation, solubility, solvation, distribution and crystal structure. International Journal of Pharmaceutics, 349: 300-312.

Rubino JT. 1988. Cosolvents and cosolvency. 375p. In: J. Swarbrick, J.C. Boylan, (Eds) Encyclopedia of Pharmaceutical Technology. New York, 1048p

Ruidiaz MA, Delgado DR, Martínez R. y Marcus Y. 2010. Solubility and preferential solvation of indomethacin in 1,4-dioxane + water solvent mixtures. Fluid Phase Equilibria, 299: 259-265.

Taylor BN y Kuyatt CE. 1994. Guidelines for evaluating and expressing the uncertainty of nist measurement results. NIST Technical Note 1297 1994 Edition, United States Departament of Comerce Technology Administration. Washington D.C, 35p.

Cómo citar
Caviedes Rubio, D. I., Rodríguez Rodríguez, G. A., & Delgado, D. R. (2016). Thermodynamic Study of the Solubility of Naproxen in Some 2-Propanol + Water Mixtures. Revista Facultad De Ciencias Básicas, 12(1), 48-55.