ExplainDissolution · Development of next-generation dissolution models for pharmaceutical tablets

The European pharmaceutical market is worth more than 200 billion euros, and a significant share of it comes from tablets, the most popular dosage form used to treat hundreds of millions of patients. The in vitro dissolution profile is used to characterize how the drug is released from tablets, indicating their effectiveness. However, an incomplete understanding of the effect of material attributes and process parameters on the dissolution profile of tablets has been the source of various quality problems for decades. These include product recalls that undermine the trust of patients in medicines and cause major financial loss. Therefore, the purpose of this proposal is to integrate advanced mechanistic modelling techniques to construct a next-generation modelling framework that predicts the dissolution profile of tablets. This will be realized by combining continuum-based modelling of tablet compression with discrete element method simulation of disintegration and population balance equation-based description of drug dissolution. The integration of these techniques requires an interdisciplinary approach and has not been done before. The resulting integrated model will consider the properties of the tablet components and the geometry of the tablet press to predict how the drug will be released from the tablet following administration. By applying this technique, we estimate that the drug development cycle can become 4-5% shorter and many quality issues can be prevented. The Fellow will undertake a non-academic placement at Pion Inc. to access state-of-the-art dissolution testing equipment with in situ UV probes for real-time concentration measurement. During the project, the Fellow will gain familiarity with the mechanistic modelling techniques described above. Combining this new knowledge with his expertise in empirical dissolution modelling will enable the Fellow to pursue an ambitious research programme in the future, greatly enhancing his academic career.