(528a) Finite-Size Effects on the Chemical Potentials of Molecular Solids
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Computational Approaches for API Process Development - Crystallization and Reaction
Wednesday, November 18, 2020 - 8:00am to 8:15am
Here we systematically examine the effect of supercell size and long-range cutoff distance on the computed chemical potentials of pharmaceutically relevant molecular crystals using classical molecular dynamics simulations. The Gibbs free energies of the crystal polymorphs and liquid phases of carbamazepine and sulfamerazine were computed from 0 K to 600 K for various system sizes and long-range cutoff radii. We compare the estimated chemical potentials with small systems and short cutoffs to those of the corresponding larger systems and show how these differences change with temperature. Furthermore, we show the effects that these small perturbations to the chemical potentials have on the macroscopic observables of enantiotropic transition temperature and solid-liquid melting temperature. Finally, we make recommendations for future molecular simulations of API crystal structures to balance the trade-off of chemical accuracy and computational efficiency.