Molecular dynamics simulation of the formation of pharmaceutical particles by rapid expansion of a supercritical solution

The formation of pharmaceutical particles by the rapid expansion of a supercritical solution is investigated by molecular dynamics simulation. As a pharmaceutical model substance naproxen, a pain reliever and anti-inflammatory drug, is used. The expansion process is modeled in the simulation method by stepwise increasing the size of the simulation box. Comparison with an accurate reference equation of state for the pure solvent carbon dioxide shows that the simulation system follows an adiabatic expansion path. The expansion of a solution of naproxen in supercritical carbon dioxide leads to a highly supersaturated system that starts to form particles. The nucleation and growth kinetics of this particle formation process is investigated and the effect on the particle structure is analyzed.