Solubility determination and three dimensional Hansen solubility parameters of gefitinib in different organic solvents: Experimental and computational approaches

Gefitinib (GFT) is an anticancer drug which shows poor aqueous solubility and bioavailability. The quantitative solubility data of GFT in any aqueous, organic or the mixture of aqueous and organic solvents have not been reported in literature. Therefore, various experimental and computational approaches for solubility determination of GFT in different organic solvents were used in the proposed research. The solubility of GFT in various organic solvents namely methanol, ethanol, isopropanol (IPA), 1-butanol, 2-butanol, ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), dimethyl sulfoxide (DMSO) and Transcutol-HP (THP) at T = 298.2 K to 318.2 K and p = 0.1 MPa was determined using an isothermal saturation shake flask method. Experimental solubilities of GFT were validated and correlated with van't Hoff and Apelblat models. Various solubility parameters for GFT and different organic solvents were also determined by HSPiP software in order to obtain the best solvents for GFT. Experimental mole fraction solubilities of GFT were recorded highest in DMSO (3.50 x 10(-2)) followed by THP (3.28 x 10(-2)), PEG-400 (3.01 x 10(-2)), 2-butanol (4.62 x 10(-3)), 1-butanol (3.80 x 10(-3)), IPA (2.94 x 10(-3)), ethanol (2.07 x 10(-3)), PG (1.64 x 10(-3)), EG (1.44 x 10(-3)) and methanol (9.23 x 10(-4)) at T = 3182 K. Similar results were also observed at T = 298.2 K, T = 303.2 K, T = 308.2 K and T = 3132 K. Various solubility parameters of GFT were found to be closet with DMSO, THP and PEG-400. The results of activity coefficients suggested maximum solute-solvent interactions in GFT-DMSO, GFT-THP and GFT-PEG-400. Based on these results, DMSO, THP and PEG-400 were optimized as the best organic solvents for miscibility/solubility of GFT. (C) 2019 Elsevier B.V. All rights reserved.