Solubilidad de farmacos

J. Chem. Eng. Data XXXX, xxx, 000

A

Thermodynamic Study of the Solubility of Procaine HCl in Some Ethanol + Water Cosolvent Mixtures
Daniel R. Delgado,† Edgar F. Vargas,‡ and Fleming Martınez*,† ´
Grupo de Investigaciones Farmaceutico-Fisicoquımicas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional ´ ´ de Colombia, A.A. 14490, Bogota D.C., Colombia, and Grupo deTermodinamica de Soluciones, Departamento de Quımica, ´ ´ ´ Facultad de Ciencias, Universidad de los Andes, Bogota D.C., Colombia ´

By using the van’t Hoff and Gibbs equations, the thermodynamic functions of Gibbs energy, enthalpy, and entropy of solution for procaine HCl in ethanol + water cosolvent mixtures were evaluated from solubility data determined at temperatures from (278.15 to 308.15) K.The drug solubility was greatest in neat water and lowest in neat ethanol at all of the temperatures studied. This behavior showed the negative cosolvent effect for this electrolyte drug in this solvent system. By means of enthalpy-entropy compensation analysis, 0-app 0-app a nonlinear ∆Hsoln versus ∆Gsoln plot with a positive slope from neat ethanol up to 0.10 mass fraction of water and negativefrom 0.10 to 0.30 mass fraction of water was obtained, whereas from this composition up to neat water a positive slope was obtained again. Accordingly to this result and to the transfer properties, it follows that the dissolution process of this drug in ethanol-rich and water-rich mixtures is enthalpydriven, whereas between 0.10 and 0.30 mass fraction of water, the process is entropy-driven.Introduction Procaine HCl (PC-HCl, Figure 1) is a local anesthetic drug used in allopathic medicine,1 as well as in neural therapy.2 Although PC-HCl is widely used nowadays in therapeutics, the physicochemical information about their aqueous solutions is not complete at present, although several physicochemical studies have been done. In this way, the solution thermodynamics in aqueous media for thisdrug has been presented in the literature.3,4 These studies have been made by using the van’t Hoff method3 and calorimetric techniques.4 On the other hand, the physical aspects of the transfer of this drug from aqueous media up to phospholipidic vesicles have also been reported.5 In a similar way, the surface tension in water has also been studied for this drug alone and in combination withphospholipidic monolayers.6 Ultimately, the apparent molar volumes in water have also been studied as a function of drug concentration and temperature.7 On the other hand, it is well-known that injectable homogeneous liquid formulations supply relatively high doses of drug in small volumes, and thus, some physicochemical properties, such as the solubility of drugs and other formulation components, arevery important, because they facilitate the design process of pharmaceutical dosage forms.8 As it has been already described, the solubility behavior of drugs in cosolvent mixtures is very important because cosolvent blends are frequently used in purification methods, preformulation studies, and pharmaceutical dosage forms design, among other applications.9,10 For these reasons, it is important todetermine systematically the solubility of pharmaceutical compounds. This information facilitates widely the labor of pharmacists associated with the research and development of new products in the pharmaceutical industry. Besides, temperaturesolubility dependence allows us to carry out the respective
* Corresponding author. E-mail: fmartinezr@unal.edu.co. † Universidad Nacional de Colombia. ‡Universidad de los Andes.

Figure 1. Molecular structure of procaine HCl. The hydrochloride form is established by the protonation of the tertiary amine group.

thermodynamic analysis, which, on the other hand, also permits inside the molecular mechanisms involved with the solution processes.11 The main objective of this study was to evaluate the effect of the cosolvent composition on the...