Solubility and Thermodynamic Analysis of Isotretinoin in Different (DMSO + Water) Mixtures

Abstract

The solubility and solution thermodynamics of isotretinoin (ITN) (3) in numerous {dimethyl sulfoxide (DMSO) (1) + water (H2O) (2)} combinations were studied at 298.2–318.2 K under fixed atmospheric pressure of 101.1 kPa. A shake flask methodology was used to determine ITN solubility, and correlations were made using the “van’t Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van’t Hoff models”. In mixtures of {(DMSO (1) + H2O (2)}, the solubility of ITN in mole fractions was enhanced with the temperature and DMSO mass fraction. The mole fraction solubility of ITN was highest in neat DMSO (1.02 × 10−1 at 318.2 K) and lowest in pure H2O (3.14 × 10−7 at 298.2 K). The output of computational models revealed good relationships between the solubility data from the experiments. The dissolution of ITN was “endothermic and entropy-driven” in all of the {(DMSO (1) + H2O (2)} mixtures examined, according to the positive values of measured thermodynamic parameters. Enthalpy was discovered to be the driving force behind ITN solvation in {(DMSO (1) + H2O (2)} combinations. ITN-DMSO displayed the highest molecular interactions when compared to ITN-H2O. The outcomes of this study suggest that DMSO has a great potential for solubilizing ITN in H2O.

Solubility and Thermodynamics Data of Cabozantinib Malate in Various Aqueous Solutions of Dimethyl Sulfoxide at Different Temperatures

“…As a result, CBZM-DMSO molecules interacted with one another more strongly than CBZM-H 2 O molecules. In several DMSO aqueous solutions as well as in neat solvents, CBZM solvated in the same manner as reported for raloxifene hydrochloride, sinapic acid, pyridazinone derivative, baricitinib, and isotretinoin [18,[25][26][27]30].…”

“…solutions as well as in neat solvents, CBZM solvated in the same manner as reported for raloxifene hydrochloride, sinapic acid, pyridazinone derivative, baricitinib, and isotretinoin [18,[25][26][27]30].…”

“…In general, it was found that the mole fraction solubilities of CBZM in pure DMSO and H 2 O were maximum and minimum, respectively. The reason why CBZM dissolves most completely in pure DMSO may be due to the weak polarity of DMSO as opposed to the strong polarity of H 2 O [28][29][30]. The higher solubility of CBZM in DMSO may also be due to intermolecular interactions between the -OH, C=O, and -MeO groups of CBZM (Figure 1A) and the S=O group of DMSO (Figure 1B).…”

“…According to reports, it lowers ligand-protein binding, which might improve the disposition of the drug's kinetic profile [22]. Many poorly soluble drugs, such as raloxifene hydrochloride, sinapic acid, pyridazinone derivatives, baricitinib, meloxicam, clozapine, and isotretinoin, have become more soluble when DMSO is used as a potential solubilizer or cosolvent [18,[25][26][27][28][29][30]. Regarding the solubility and thermodynamic data of CBZM in different {DMSO + H 2 O} mixes at varying temperatures and constant ambient/atmospheric pressure, there is no information available in the literature.…”