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.

Environmentally friendly stability-indicating HPLC method for the determination of isotretinoin in commercial products and solubility samples

“…At 25 °C, the mole fraction solubility of ITN in water, MeOH, EtOH, EG, PG, PEG-400, EA, and DMSO was determined to be 3.18 × 10 −7 , 4.43 × 10 −4 , 8.09 × 10 −4 , 6.24 × 10 −4 , 1.10 × 10 −3 , 5.58 × 10 −3 , 8.84 × 10 −3 , and 8.62 × 10 −2 , respectively. At 25 °C, the mole fraction solubility of ITN in water, MeOH, EtOH, EG, PG, PEG-400, EA, and DMSO has been reported as 3.16 × 10 −7 , 4.45 × 10 −4 , 8.06 × 10 −4 , 6.27 × 10 −4 , 1.07 × 10 −3 , 5.56 × 10 −3 , 8.82 × 10 −3 , and 8.64 × 10 −2 , respectively [ 13 ]. ITN had solubility values that were consistent with those reported in the literature in a number of environmentally friendly solvents [ 13 ].…”

“…At 25 °C, the mole fraction solubility of ITN in water, MeOH, EtOH, EG, PG, PEG-400, EA, and DMSO has been reported as 3.16 × 10 −7 , 4.45 × 10 −4 , 8.06 × 10 −4 , 6.27 × 10 −4 , 1.07 × 10 −3 , 5.56 × 10 −3 , 8.82 × 10 −3 , and 8.64 × 10 −2 , respectively [ 13 ]. ITN had solubility values that were consistent with those reported in the literature in a number of environmentally friendly solvents [ 13 ]. These findings indicated that ITN solubility in various solvents may be determined using the current methodology.…”

“…Recently, a practical method for administering ITN orally to pediatric patient with neuroblastoma has been suggested [ 12 ]. It is a highly hydrophobic compound, which creates the difficulties in its dosage form design [ 13 ].

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

“…The solid-phase characterization of ITN before solubility determination (pure ITN) and after solubility determination (equilibrated ITN) was carried out to investigate the possibility of ITN evolving into polymorphs or solvates/hydrates. The findings of this characterization on pure and equilibrated ITN using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transforms infrared spectroscopy (FTIR) investigations are presented in our most recent work [33]. The FTIR, DSC, and PXRD spectra of both samples of ITN were said to be similar and to exhibit similar peak characteristics in our most recent paper [33].…”

“…The solubility of ITN in a few environmentally friendly solvents, such as propylene glycol (PG), polyethylene glycol-400 (PEG-400), and carbitol, has been documented at room temperature [28,31]. At temperatures ranging from 298.2 to 318.2 K and an atmospheric pressure of 101.1 kPa, we previously reported the solubility and thermodynamic data of ITN in 11 distinct green solvents, namely H2O, methanol, ethanol, 1-butanol, 2butanol, ethylene glycol, PG, PEG-400, ethyl acetate, carbitol, and DMSO [33]. The stock solution of DMSO has been utilized as a de facto standard for the storage of numerous substances and the distribution of various assays, including solubility assessment [34].…”