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Model predictive in vitro dissolution testing in pharmaceutical continuous manufacturing: An equivalence study |
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| Authors: | Qinglin Su Paul Hermant Federica Casati Bhakti Halkude Wei Wu Anjana Ramnath Atul Dubey Stephen Born Bayan Takizawa Salvatore Mascia |
| Affiliation: | 1. CONTINUUS Pharmaceuticals, Woburn, Massachusetts, USA;2. CONTINUUS Pharmaceuticals, Woburn, Massachusetts, USA Contribution: Data curation (equal), Investigation (equal), Writing - review & editing (equal);3. CONTINUUS Pharmaceuticals, Woburn, Massachusetts, USA IMA S.p.A., Bologna, Italy Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - review & editing (equal);4. CONTINUUS Pharmaceuticals, Woburn, Massachusetts, USA Contribution: Data curation (equal), Writing - review & editing (equal);5. United States Pharmacopeia, Rockville, Maryland, USA Contribution: Project administration (equal), Writing - review & editing (equal);6. CONTINUUS Pharmaceuticals, Woburn, Massachusetts, USA Contribution: Project administration (equal), Writing - review & editing (equal);7. CONTINUUS Pharmaceuticals, Woburn, Massachusetts, USA Contribution: Funding acquisition (equal), Project administration (equal), Writing - review & editing (equal) |
| Abstract: | 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 f2 > 50 for all sampled tablets. Concluding remarks and industrial perspectives on model predictive in vitro dissolution testing are provided. |
| Keywords: | dissolution equivalence mathematical models real-time release tablets |