Constructing Mesoscale Models with Smolyak Sparse Grids
AIChE Annual Meeting
2023
2023 AIChE Annual Meeting
Computational Molecular Science and Engineering Forum
Poster Session: Computational Molecular Science and Engineering Forum
Monday, November 6, 2023 - 3:30pm to 5:00pm
48 of the investigated examples can be explained by only two classes of impurity retention mechanisms. The most common mechanism at 79% of cases related to when the impurity is miscible in the solid state with the product and forms one solid solution phase, or in some cases two solid solution phases (one where the impurity is the minor component, and the second phase where the product is the minor component). This outcome was found across the board, independent of pharmaceutical company, academia or type of compound. The second most common impurity retention mechanism at 21%, related to when phase-pure impurities crystallized during the cycle time of the process, resulting in a physical mixture with the product. These can be further separated into SLIP 1 (17%) or SLIP 2 (4%) mechanisms2. In no case were solvent inclusion, agglomeration, surface adsorption or co-crystals identified as the responsible mechanism. The reasons for the results are discussed based on a thermodynamic assessment including ternary phase diagrams, practical scale-up constraints, and a critical assessment on the theoretical impurity retention mechanisms.
[1] Nordstrom, Sirota, Hartmanshenn, Kwok, Paolello, Li, Abeyta, Bramante, Madrigal, Behre, Capellades, Org. Proc. Res. & Dev., 2023
[2] Nordstrom, Linehan, Teerakapibal, Li, Cryst. Growth. Des. 2019, 19, 1336-1346