Study of the Effects of Alcohols as Co-Solvents on the Interaction of Drugs with Carbon Dioxide in Supercritical Conditions by Molecular Dynamics

The density of studied systems was calculated at different temperatures and pressures andrelative error values were obtained. The results show good agreement with experimental data.Using the molecular dynamics simulation, the effect of methanol, ethanol and propanol solventson the interaction of CO2 with methimazole, propranolol and phenazopyridine was studied undersubcritical and supercritical conditions. For this purpose, the charmm27 all-atom field and theGromacs software were employed. The radial distribution function of various atoms of drugs andcarbon and oxygen of carbon dioxide was calculated. The results revealed that methanol alteredthe aggregation of CO2 around phenazopyridine in supercritical conditions and increasedaggregation, while for methimazole and propranolol, propanol co-solvent was more effectivethan other two alcohols on the aggregation of CO2 around the drug. In addition, the aggregationof solvents around phenazopyridine occures more than two other drugs. The analysis of weakinteractions was performed based on Local Orbital Localization and it was determined thathydrogen interactions and steric effects of the drug ring and cage structures of CO2 play a greaterrole than the Van der Waals interaction.

Keywords:

Molecular Dynamics , Co-Solvent Effects , Supercritical Carbon Dioxide