(139e) Combining Simulation and Experiment to Understand Polymorph Selection of Drug Molecules in Different Solvents
- Conference: AIChE Annual Meeting
- Year: 2018
- Proceeding: 2018 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
Monday, October 29, 2018 - 2:10pm-2:35pm
In this work, we combined simulations and experiments to study the nucleation of small molecules in different solvents. As the Ostwaldâs rule stated that the polymorph with a lower nucleation energy barrier always crystallizes first in general, our simulations could provide information on polymorph selection that are consistent with the experimental data. Two polymorphs of sulfamerazine (Form I and II), and three different solvents, water, methanol and acetonitrile, were selected for our study. By implementing the String Method in Collective Variables (SMCV) in combination with the construction of order parameters, we sketched the minimum free energy paths of nucleation and calculated the energy barriers for both of the two forms. Simulation results showed that Form I has lower energy barriers in all the solvents than Form II, indicating that Form I would be easier to nucleate. PXRD data from our crystallization experiments showed consistent results that Form I was the favorable form in these solvents.