Solid–Liquid Equilibrium of Molnupiravir in 15 Monosolvents: An Experimental and Molecular Simulation Study

Molnupiravir (MPV) has a strong antiviral effect. However, there are few existing reports on the solubility properties of this drug. In this article, the solubility of MPV in 15 monosolvents was measured using the gravimetric method. Among all experimental solvents, the solubility of MPV was found to be the highest in cyclohexanone and the lowest in ethyl formate. In alcohol solvents, the maximum solubility was observed in s-butanol, while the minimum value was observed in i-butanol. The solubility of MPV increases with an increase in the temperature. Thermodynamic models including the modified Apelblat model, λh model, Yaws model and Abolghasem Jouyban model were chosen to fit the solubility data in 15 monosolvents. The Abolghasem Jouyban model fitted the experimental data best among all the selected models in 15 monosolvents, with relative average deviation (RAD) = 0.0024. Finally, a molecular dynamics simulation, radial distribution function (RDF) analysis, and density functional theory (DFT) calculation were performed. The results indicated that MPV could interact with organic solvents via van der Waals interactions, electrostatic interactions, and hydrogen bonding. The experimental data for MPV will provide significant guidance for the optimization of the crystallization process.