Thermodynamic analysis of celecoxib in amphiprotic and amphiprotic-aprotic solvent mixtures at several temperatures

Abstract

The solubilities of celecoxib (CLX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water-ethanol and ethanol-ethyl acetate mixtures at several temperatures (288.15-308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures, they showed a single maximum located at 50% ethanol-ethyl acetate (δ1 = 22.50 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs free energy of solution (ΔHS,ΔSS and ΔGShm, respectively). The apparent enthalpies of the solution were a nonlinear function of the ethanol ratio in aqueous mixture. Non-linear enthalpy-entropy compensation analysis was observed indicating different dissolution mechanism with the variation in mixtures composition. The solubility enhancement is entropy driven at water-rich region (0-40% v/v ethanol) and enthalpy controlled at ethanol-rich region (40–100% v/v ethanol), likely due to water-structure loss around nonpolar moieties of the drug and for the ethanol-rich mixtures it is the enthalpy, probably due to the drug better solvation.

The Applications of food hydrocolloids in drug delivery system

“…HPMC is a cellulose ether produced from cellulose, methyl chloride, and propylene oxide in a base-catalyzed heterogeneous process [54]. HPMC is soluble in water or water/solvent mixtures and can be dissolved in nonaqueous solvents with medium to high polarity [55]. The FDA has classified HPMC as GRAS, based on toxicity assessments using oral and intraperitoneal delivery methods.…”