title: Solubility and thermodynamics of apremilast in different mono solvents: Determination, correlation and molecular interactions.
abstract: 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=298.2K to 318.2K" 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 254nm. 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=318.2K" 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.
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Center of Excellence in Biotechnology Research (CEBR), King Saud University, P.O. Box 2460, Riyadh 11451, Saudi Arabia. Electronic address: faiyazs@fastmail.fm.
authors.forename: Faiyaz
authors.initials: F
authors.lastname: Shakeel
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Nazrul
authors.initials: N
authors.lastname: Haq
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Fars K
authors.initials: FK
authors.lastname: Alanazi
authors.affiliation: Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Alsarra
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012997:Solvents; D013792:Thalidomide; C505730:apremilast
keywords: Activity coefficient; Antipsoriatic arthritis; Apremilast; Dissolution thermodynamics; Mono solvent; Solubility