Polylactide nanoparticle impregnation with carbamazepine in supercritical media and its subsequent release in liquid solvents: insights from molecular simulation

Journal of Molecular Liquids. 2022. Vol. 352. Article 118758.

Gurina D., Budkov Y., Kiselev M. G.

A full-atomic classical molecular dynamics simulation of polylactide nanoparticle impregnation with carbamazepine in supercritical carbon dioxide was performed. The effect of temperature (333 K, 373 K), pressure (20 MPa, 40 MPa) and ethanol addition (1.7 mol.%) on the impregnation process was studied. Based on the solvent accessible surface area values it was concluded that a pressure increase and cosolvent addition have a positive effect on polymer swelling, and a temperature increase at a similar pressure value has a negative effect. It was demonstrated that carbamazepine gets adsorbed on the polymer nanoparticle surface and penetrates inside the polymer matrix. The main interaction sites were determined. The average number and lifetime of hydrogen bonds, the solute mobility before and after the impregnation process were estimated. The possibility of carbamazepine release from the polylactide nanoparticle in water, ethanol and dichloromethane was studied at 310 K and 0.1 MPa. Since the drug and polymer affinities to the solvents are not equal, their release behavior is completely different.

Keywords: supercritical fluids, сверхкритические флюиды, molecular dynamics, классическая молекулярная динамика, Swelling, Набухание полимеров, drug compounds, лекарственные соединения