Thermodynamics and transport properties of gabapentin, paracetamol, & albuterol in water

The solubility and dissolution rates of drugs are significantly influenced by factors such as solvation-free energy and diffusion coefficient , which are essential for understanding their transport and thermodynamic properties. In this study, we investigated the free energy and transport properties of various drug molecules using classical molecular dynamics simulations . The systems were modeled using the OPLS force field. Solvation-free energies for paracetamol , gabapentin , and albuterol in water (TIP3P & TIP4P/2005 models) were computed at 310 K using thermodynamic integration (TI) and free energy perturbation (FEP) based methods across 21 coupling constant ( λ ) values. Additionally, solvent-accessible surface area (SASA) and hydrogen bond analyses provided further insights into the solvation behavior of these drugs. The diffusion coefficients were calculated using Einstein's and Darken's relations. The self-diffusion coefficients of the drugs and SPC/E water at 310 K showed good agreement with experimental data. Additionally, the shear viscosity of the drug-water solution has been studied using Einstein's relation. The structural properties of the system were analyzed using the radial distribution function (RDF) of different atomic pairs in solvent and solute. This work provides insights into the solvation and transport behavior of drug molecules, aiding in the understanding of their physicochemical properties. • Solvation-free energy of Gabapentin, Paracetamol, and Albuterol was estimated using TI and FEP. • RDF, hydrogen bonding, and SASA analysis revealed key solute-solvent interactions influencing solvation behavior. • Self-diffusion coefficients and shear viscosity were computed to understand solute transport in aqueous environments.