(381d) Anticipate and Avoid Oiling out in Crystallization Using Molecular Dynamics Simulations
- Conference: AIChE Annual Meeting
- Year: 2018
- Proceeding: 2018 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Tuesday, October 30, 2018 - 4:35pm-4:55pm
We have used molecular dynamics simulations for this purpose. We ran a series of simulations with the supersaturated solute in the presence of varying quantities of anti-solvent to investigate the differences in nucleated structures between onset of crystallization and oil-out phases. The simulations demonstrate that system can be triggered to nucleate into a separate liquid phase rather than forming a solid phase depending on the interfacial energy of the nucleated or seeded crystals. If the energy is favorable for adsorption of the âoilâ molecules rather than API molecules, the system oils out.
We have identified conditions, such as solvent composition, mode of addition, degree of supersaturation, etc., that favor adsorption of one species over another to predict âoiling outâ following a simple thermodynamic-and-kinetic model.
In our study, we used this approach to verify robustness of the crystallization protocol. In addition, the method also illustrates an example of the quality-by-design (QbD) approach where a range of crystals can be produced with varied particle size distribution by making small modifications to the procedure thereby avoiding oiling out.