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

• This study investigates solubilities of etodolac and enhancements of them by adding co-solvents.
• Six cyclodextrins (CDs): α, β, γ-CD, 2-HP-β-CD, 2-HE-β-CD, and M-β-CD were investigated as co-solvent.
• Solubilities of etodolac containing water/co-solvent mixtures were measured using HPLC at 298 K.
• The solubilization power and stability constant for five co-solvents were evaluated.
• It can be concluded that chemically modified CDs are more suitable co-solvents than natural CDs.

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 298.15 K in mixtures of water and the following six cyclodextrins (CDs) using high-performance liquid chromatography: α-CD, β-CD, γ-CD, 2-hydroxypropyl-β-CD, 2-hydroxyethyl-β-CD, and methyl-β-CD. With the exception of γ-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.