(721a) Application of CFD Integrated Dissolution Model in Biological Product Formulation Process

The dissolution process is widely used in biological product formulation development. Since a large number of compounds/excipients may be involved, a model, which is capable of predicting particle dissolution performance in selection of right compound/excipient and mixing system, is particularly desirable to minimize the amount of experimental work in biological product formulation development, scale up / down and tech transfer. A CFD integrated dissolution model was developed. The model combines CFD simulation and Noyes–Whitney equation. The energy dissipation rate of the dissolution system is linked with particle mass transfer rate through the Sherwood number, which is obtained by CFD simulation. The model was validated by the literature data. The model also can be used to evaluate effect of particle size, density, solubility and diffusivity, amount of compound/excipient, impeller size and shape, tank size, mixing speed and time on the dissolution performance. Further the scale down model workflow was developed to investigate the impact of material properties, process parameters and impeller size and shape on the dissolution behaviors in commercial scale mixing tank. Two case studies were presented: 1 evaluate impact of the particle properties ( DTPA vendor change) on dissolution behavior in 4 commercial scale buffer formulation tanks and 2. evaluate impact of impeller configuration (Different size and shape impellers with/without vortex breaker) on dissolution behavior in a protein formulation tank using only 35 ml protein/vessel. The CFD integrated dissolution model and scale down model workflow were demonstrated successful in predicting dissolution behavior in biologic product commercial scale tank and supporting CAPA decision making. The simulation results also were implemented in manufacture sites.