Solubilization and Thermodynamic Analysis of Isotretinoin in Eleven Different Green Solvents at Different Temperatures

Abstract

The solubilization and thermodynamic analysis of isotretinoin (ITN) in eleven distinct green solvents, such as water, methyl alcohol (MeOH), ethyl alcohol (EtOH), 1-butyl alcohol (1-BuOH), 2-butyl alcohol (2-BuOH), ethane-1,2-diol (EG), propane-1,2-diol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO) was studied at several temperatures and a fixed atmospheric pressure. The equilibrium approach was used to measure the solubility of ITN, and the Apelblat, van’t Hoff, and Buchowski–Ksiazczak λh models were used to correlate the results. The overall uncertainties were less than 5.0% for all the models examined. The highest ITN mole fraction solubility was achieved as 1.01 × 10−1 in DMSO at 318.2 K; however, the least was achieved as 3.16 × 10−7 in water at 298.2 K. ITN solubility was found to be enhanced with an increase in temperature and the order in which it was soluble in several green solvents at 318.2 K was as follows: DMSO (1.01 × 10−1) > EA (1.73 × 10−2) > PEG-400 (1.66 × 10−2) > THP (1.59 × 10−2) > 2-BuOH (6.32 × 10−3) > 1-BuOH (5.88 × 10−3) > PG (4.83 × 10−3) > EtOH (3.51 × 10−3) > EG (3.49 × 10−3) > MeOH (2.10 × 10−3) > water (1.38 × 10−6). ITN–DMSO showed the strongest solute–solvent interactions when compared to the other ITN and green solvent combinations. According to thermodynamic studies, ITN dissolution was endothermic and entropy-driven in all of the green solvents tested. The obtained outcomes suggested that DMSO appears to be the best green solvent for ITN solubilization.