Solubility of simvastatin: A theoretical and experimental study

• Published in: Journal of molecular structure Vol. 995; no. 1; pp. 41 - 50
• Main Authors: Aceves-Hernández, Juan M., Hinojosa-Torres, Jaime, Nicolás-Vázquez, Inés, Ruvalcaba, Rene Miranda, García, Rosa María Lima
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 31-05-2011
• Subjects: Alcohols; Density functional theory; Dielectric constant; Enthalpy; Ethanol; Ethyl alcohol; Mathematical analysis; Mathematical models; Simvastatin; Solubility; Solvents; Theoretical calculations; Density functional theory; Theoretical calculations; Simvastatin; Enthalpy; Solubility; Alcohols
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2011.03.048

► Solvation process slightly change Simvastatin struture in space. ► Simvastatin charge distributions correspond to simvastatin dipole moments in different solvents. ► Dielectric constant vs. Gibss free energy plot is very similar to solubility vs. alcohols family length.
Solubility experimental data from Simvastatin in a family of alcohols were obtained at different temperatures. Simvastatin was characterized by using thermal analysis and X-ray diffraction. From the experimental solubility data an anomalous behavior was observed, since an increase the number of alcohol carbon atoms shows an increase in solubility only for the three first alcohols, ethanol, 1-propanol and 1-butanol. A decrease in solubility was obtained for 1-pentanol, 1-hexanol and 1-octanol. Van’t·Hoff equation was used to obtain the theoretical solubility value and the ideal activity coefficient. Experimental error was very low and does not affect the plots and equations used. No polymorphic phenomenon was found from the Simvastatin characterization. Theoretical calculations were carried out in order to corroborate the experimental solubility data. Trends and results are similar in both cases. The geometry optimizations of Simvastatin was carried out using density functional theory with Becke’s three parameter hybrid method and correlation functional of Lee, Yang and Parr (B3LYP) with 6-311++G∗∗ basis set. The solvent effect was treated using a continuum model as modeled in water, methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol and 1-octanol. Moreover, dielectric constant, dipolar moment and solubility in the solvents were obtained for explaining the former behavior.