Measurement and correlation of solubilities of the poorly water-soluble pharmaceutical compound etodolac by addition of co-solvents

The purpose of this study is to measure the solubilities of poorly water-soluble drugs, and to enhance their solubilities by adding co-solvents. Etodolac, a cyclooxygenase-2 (cox-2) inhibitor in non-steroid anti-inflammatory drugs (NSAIDs), was selected as a model pharmaceutical compound. The solubilities of etodolac were determined at 298.15K in mixtures of water and the following six cyclodextrins (CDs) using high-performance liquid chromatography: alpha-CD, beta-CD, gamma-CD, 2-hydroxypropyl-beta-CD, 2-hydroxyethyl-beta-CD, and methyl-beta-CD. With the exception of gamma-CD, the experimental solubility data were correlated using a modified Chrastil model. Additionally, the solubilization power of each correlated co-solvent-solute system was evaluated using a log-linear model. Finally, the stability constants were determined using the Takeru Higuchi-Connors solubility method. (C) 2013 Elsevier B.V. All rights reserved,