Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485645 | Journal of Pharmaceutical Sciences | 2012 | 11 Pages |
Abstract
This study investigates the cosolute effects of mefenamic acid (XA) and flufenamic acid (FA). These compounds serve as model of a drug discovery lead compound and a structural analogue. The activity coefficients of XA and FA in different solvents were obtained from solubility measurements at 25°C. The effect of varying concentrations of FA on the solubility of XA in four different solvents, including toluene, cyclohexane, ethanol, and an ethanol-water mixture (80:20, v/v), was investigated. The magnitude of change in the activity coefficient of XA in the presence of FA in different solvents was used to elucidate the thermodynamic effect of FA on the solubility of XA. Nuclear magnetic resonance and Fourierâtransform infrared spectroscopy were used to obtain molecular level information about the interactions of the compounds in solution. The presence of FA increases XA solubility in toluene and in cyclohexane as much as sevenâfold. Conversely, in ethanol and the ethanol-water mixture, similar levels of FA have essentially no effect on the solubility of XA. The solution properties investigated show that despite the close structural similarity between XA and FA, the two compounds are strongly distinguishable in nonpolar solvents. Conversely, the solution properties of the same two solutes are indistinguishable in polar solvents. A solubilization model based on soluteâcosolute interactions is presented.
Keywords
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Eun Hee Lee, Stephen R. Byrn, Rodolfo Pinal,