Thermodynamic Study of the Solubility of Procaine HCl in Some Ethanol + Water Cosolvent Mixtures

Abstract

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, a nonlinear ∆H soln 0-app versus ∆G soln 0-app plot with a positive slope from neat ethanol up to 0.10 mass fraction of water and negative from 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.

Thermodynamic study of the solubility of sodium naproxen in some ethanol + water mixtures

“…6 The main objective of this study was to evaluate the effect of the cosolvent composition on the solubility and solution thermodynamics of Na-NAP in ethanol (EtOH) + water cosolvent mixtures based on the van't Hoff method as has been done earlier with procaine hydrochloride. 8 Thus, this investigation amply the information reported by Chavez about the solubility of this drug in the same cosolvent system. 4 …”

“…If the inter-ionic interactions are not considered, in a first approach the v value could be ideally assumed as 2 for this saline drug, and thus, this value could be used to calculate the apparent thermodynamic functions of solution. 8,10 Thermodynamic functions of solution According to van ( 1) where, R is the universal gas constant (8.314 J mol -1 K -1 ). As an example, Figure 2 shows the modified van't Hoff plot for Na-NAP in mixtures containing 0.40, 0.60, and 0.80 in mass fraction of EtOH.…”

“…If the addition of EtOH to neat water is considered (being the cosolvent mixture less polar as the EtOH proportion increases), as has been done earlier, 8 it happens the following, from pure water to 0.20 in mass fraction of EtOH (∆G A→B 0-app < 0, ∆H A→B 0-app > 0, and ∆S A→B 0-app > 0) the solubility process is driven by the entropy; whereas, from this composition up to 0.50 in mass fraction of EtOH (∆G A→B 0-app < 0, ∆H A→B 0-app < 0, and ∆S A→B 0-app < 0) the dissolution process is enthalpy driven. Ultimately, from this EtOH proportion up to neat EtOH (∆G A→B 0-app > 0, ∆G A→B 0-app < 0, and ∆S A→B 0-app < 0), the solution process is entropy driven, again.…”

The Importance of Dielectric Constant for Drug Solubility Prediction in Binary Solvent Mixtures: Electrolytes and Zwitterions in Water + Ethanol

“…Available solubility data for electrolytes and zwitterions in water+ethanol mixtures were extracted from the literature (1,4,8). The criterion for inclusion in selected data was the availability of solubility data in water and ethanol, where…”

“…The main pattern of solubility behavior in water +ethanol mixture has a maximum of solubility in ethanol-rich area for most of the non-electrolyte solutes (1,2). This pattern is not the same for ionizable compounds in water such as sodium salts of medicines and amino acids where the solubility value in water is more than solubility value in neat ethanol (4).…”