Thermodynamic analysis of the solubility of progesterone in 1-octanol + ethanol cosolvent mixtures at different temperatures

• Published in: Alexandria engineering journal 2023-02, Vol.64, p.219-235
• Main Authors: Torres-Cardozo, Andrea, Cerquera, Nestor Enrique, Ortiz, Claudia Patricia, Osorio-Gallego, Jhonny, Cardenas-Torres, Rossember Edén, Angarita-Reina, Fredy, Martinez, Fleming, Delgado, Daniel Ricardo
• Format: Article
• Language: English
• Subjects: Cosolvent mixtures; Progesterone; Solubility model; Thermodynamic solutions
• ISSN: 1110-0168
• DOI: 10.1016/j.aej.2022.08.035

Thermodynamic studies of drug solubility in cosolvent mixtures at different temperatures generate information of great importance for pharmaceutical, medical, and environmental sciences. The objective of this research is to thermodynamically analyze the solubility of progesterone (PG) in cosolvent mixtures {1-octanol (1) + ethanol (2)} from 278.15 K to 318.15 K (nine study temperatures). The solubility of progesterone (in mole fraction) increased with the addition of 1-octanol to the cosolvent mixture, presenting its lowest value (3.474 ± 0.03 × 10-3) in pure ethanol (EtOH) at 278.15 K and its highest value (132.4 ± 3.0 × 10-3) in pure 1-octanol (OCT) at 318.15 K. The solution process of progesterone is endothermic and is driven by the enthalpy of solution. Regarding the thermodynamics of the mixture, the increase in the 1-octanol concentration favors the formation of the cavity and therefore the increase in the solubility of the progesterone. According to the entropic enthalpy compensation (EEC) analysis, it is corroborated that the solution process is driven by enthalpy. Finally, seven models (Apelblat, λh, Yaws, NRTL, Wilson and modified Wilson) were evaluated, which presented MRD% less than 1.0, which demonstrated a good correlation between the data obtained with each of the models and the data obtained experimentally.