Estudio termodinámico de la solubilidad y solvatación preferencial de meloxicam y piroxicam en mezclas Acetato de Etilo + Etanol
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Cristancho Bautista, Diana Marcela
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En el presente trabajo se presenta la información relacionada con el estudio termodinámico de la disolución y solvatación de los fármacos antiinflamatorios no esteroideos Meloxicam y Piroxicam en mezclas solventes acetato de etilo + etanol a diferentes temperaturas, como un aporte al entendimiento de éstos procesos y a complementar la información fisicoquímica de estos sistemas de interés farmacéutico. A partir de los datos de solubilidad experimental de los fármacos Meloxicam y Piroxicam en nueve mezclas solventes acetato de etilo + etanol y en los dos solventes puros, mediante la aplicación de las ecuaciones de van´t Hoff y Gibbs, se determinaron las funciones termodinámicas de los procesos de disolución y mezcla de estos fármacos. Se encontró una dependencia de la solubilidad de ambos fármacos con la composición de las mezclas y la temperatura. El incremento en la proporción de acetato de etilo en el medio incrementa la solubilidad de ambos fármacos, siendo en mezclas solventes de alta proporción de éste solvente donde se alcanza la máxima solubilidad. Los resultados de las funciones termodinámicas del proceso de solución y mezcla fueron analizadas en términos de las interacciones soluto-soluto, solvente-solvente y solutosolvente para cada sistema. Se encontró que el proceso de solución es endotérmico y conducido por la entropía. A través de la aplicación del método de las integrales inversas de Kirkwood-Buff, se determinaron los parámetros de solvatación preferencial por el acetato de etilo para ambos fármacos en las mezclas solventes. Los resultados indican una dependencia no lineal de los parámetros con la proporción de acetato de etilo en las mezclas, favoreciéndose la solvatación de ambos fármacos por el acetato de etilo en mezclas de composición intermedia.
Abstract. In this work information related to thermodynamic behavior of the dissolution and solvation of NSAIDs Meloxicam and Piroxicam in ethyl acetate + ethanol solvent mixtures at different temperatures is presented. This is as a contribution to understand these processes and complement the physicochemical information of these systems of pharmaceutical interest. From experimental data of solubility of Meloxicam and Piroxicam in nine solvent mixtures conformed by ethyl acetate + ethanol and both pure solvents, and using van't Hoff and Gibbs equations, the thermodynamic functions of solution and drug mixing were determined. A dependence of the solubility of both drugs with the composition of the mixtures and temperature was found. The solubility of both drugs increases when the proportion of ethyl acetate in the medium increases. Maximum solubility is reached in an ethyl acetate-rich mixture solvent. The results of thermodynamic functions of solution and mixing were analyzed in terms of solute-solute, solvent-solvent and solute-solvent interactions for each system. It was found that the solution process is endothermic and entropy-driven. Preferential solvation parameters by ethyl acetate for both drugs in the solvent mixtures were determined by the application of the method of inverse Kirkwood-Buff integrals. The results show a non-linearly dependence of preferential solvation parameters with the ethyl acetate proportion in the solvent mixtures; these drugs are solvated in a preferential way by ethyl acetate in mixtures of similar solvent composition.
Abstract. In this work information related to thermodynamic behavior of the dissolution and solvation of NSAIDs Meloxicam and Piroxicam in ethyl acetate + ethanol solvent mixtures at different temperatures is presented. This is as a contribution to understand these processes and complement the physicochemical information of these systems of pharmaceutical interest. From experimental data of solubility of Meloxicam and Piroxicam in nine solvent mixtures conformed by ethyl acetate + ethanol and both pure solvents, and using van't Hoff and Gibbs equations, the thermodynamic functions of solution and drug mixing were determined. A dependence of the solubility of both drugs with the composition of the mixtures and temperature was found. The solubility of both drugs increases when the proportion of ethyl acetate in the medium increases. Maximum solubility is reached in an ethyl acetate-rich mixture solvent. The results of thermodynamic functions of solution and mixing were analyzed in terms of solute-solute, solvent-solvent and solute-solvent interactions for each system. It was found that the solution process is endothermic and entropy-driven. Preferential solvation parameters by ethyl acetate for both drugs in the solvent mixtures were determined by the application of the method of inverse Kirkwood-Buff integrals. The results show a non-linearly dependence of preferential solvation parameters with the ethyl acetate proportion in the solvent mixtures; these drugs are solvated in a preferential way by ethyl acetate in mixtures of similar solvent composition.