Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study

A predictive mathematical model for tablet dissolution was developed and implemented in an end-to-end integrated continuous manufacturing pilot plant. The tablets were produced for immediate release with a proprietary extrusion-molding-coating (EMC) unit operation. Besides the mass balance of API solute in the buffer solution, the model consisted of the dissolution, diffusion, and population balance of API particles in the swollen tablet, which was mainly controlled by the swelling and erosion of the polymeric excipient matrix. An equivalence study was investigated by comparing the model prediction to the experiments that were conducted according to USP42-NF37 General Chapter < 711 > Dissolution, during which the drug dose level was varied in a range from 60 to 80 wt%. Consistent equivalence was demonstrated with the similarity factor f(2) > 50 for all sampled tablets. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided.

Automated summary

A predictive mathematical model was developed and implemented in a continuous manufacturing pilot plant for tablet dissolution. The model included the mass balance of API solute and the dissolution, diffusion, and population balance of API particles in the swollen tablet. Equivalence was demonstrated through comparison with experimental data, with all sampled tablets showing a similarity factor f(2) > 50. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided.