Solubilization of a novel antitumor drug ribociclib in water and ten different organic solvents at different temperatures.

OBJECTIVE

This study reports new solubility and physicochemical data for ribociclib (RCB) in water and ten organic solvents including "methanol (MeOH), ethanol (EtOH), isopropyl alcohol (IPA), n-butanol (n-BuOH), propylene glycol (PG), polyethylene glycol-400 (PEG-400), acetone, ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)" at 293.2-313.2 K and 101.1 kPa.

SIGNIFICANCE: The obtained data are useful for the industrial applications of RCB.

METHODS

The solubility of RCB was measured and regressed using "van't Hoff, Buchowski-Ksiazczak λh, the modified Apelblat, and Jouyban models."

RESULTS

The overall deviations of <4.0% were recorded for all four models. The maximum mole fraction solubility of RCB was 2.66 × 10-2 in PEG-400 at 313.2 K, however, the lowest one was in the water. The RCB solubility increased with temperature and the order followed in the water and ten different organic solvents was PEG-400 (2.66 × 10-2) > THP (1.00 × 10-2) > PG (5.39 × 10-3) > DMSO (5.00 × 10-3) > n-BuOH (3.23 × 10-3) > acetone (3.11 × 10-3) > IPA (1.58 × 10-3) > EA (1.41 × 10-3) > EtOH (1.37 × 10-3) > MeOH (8.10 × 10-4) > water (2.38 × 10-5) at 313.2 K. The maximum solute-solvent interactions were found in RCB-PEG-400 in comparison with other combination of RCB and solvents. "Apparent thermodynamic analysis" indicated an "endothermic and entropy-driven dissolution" of RCB in water and ten organic solvents.

CONCLUSIONS

Based on all these data and observations, PEG-400 can be used as the best co-solvent for RCB solubilization.