Solubility and thermodynamics of apremilast in different mono solvents: Determination, correlation and molecular interactions
The solubility data of recently launched poorly soluble antipsoriatic drug apremilast (APM) in any mono solvent or cosolvent mixtures with respect to temperature are not available in literature. Hence, in this research work, the solubility of APM in twelve different mono solvents namely “water, methanol, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol®” was determined at temperatures “T = 298.2 K to 318.2 K” and pressure “p = 0.1 MPa”. Eexperimental solubilities of APM in mole fraction were determined by a static equilibrium method using high performance liquid chromatography at 254 nm. Experimental solubilities of APM in mole fraction were correlated well with “Van't Hoff and Apelblat models”. The solubilities of APM in mole fraction were recorded highest in DMSO (9.91 × 10−2), followed by EA (2.54 × 10−2), Transcutol (2.51 × 10−2), PEG-400 (2.16 × 10−2), PG (4.01 × 10−3), EG (1.61 × 10−3), IPA (4.96 × 10−4), 1-butanol (4.18 × 10−4), 2-butanol (3.91 × 10−4), methanol (2.25 × 10−4), ethanol (2.20 × 10−4) and water (1.29 × 10−6) at “T = 318.2 K” and similar results were also obtained at each temperature evaluated. The molecular interactions between solute and solvent molecules were evaluated by the determination of activity coefficients. Based on activity coefficients, the higher solute-solvents molecular interactions were recorded in APM-DMSO, APM-EA, APM-Transcutol and APM-PEG-400 in comparison with other combination of solute and solvents. “Apparent standard thermodynamic parameters” of APM indicated an “endothermic and entropy-driven dissolution” of APM in all mono solvents evaluated. Based on these results, APM was proposed as freely soluble in DMSO, EA and Transcutol, sparingly soluble in PEG0-400, slightly soluble in methanol, ethanol, IPA, EG, PG, 1-butanol and 2-butanol and practically insoluble in water. Hence, DMSO, EA and Transcutol were selected as the best solvents and water and ethanol were selected as the anti-solvents for APM.