Development of next-generation dissolution models for pharmaceutical tablets

Descripción del proyecto

Modelización de la disolución de fármacos en comprimidos

La mayoría de los fármacos se presentan en forma de comprimidos. Sin embargo, sigue siendo complicado predecir cómo se disuelven y se liberan en el organismo. El perfil de disolución depende de interacciones complejas entre los materiales y las condiciones de fabricación, y es fundamental para evaluar la eficacia del fármaco. Un control deficiente de estos factores puede provocar la retirada de productos y minar la confianza del público. El proyecto ExplainDissolution, que cuenta con el apoyo de las acciones Marie Skłodowska-Curie, tiene como objetivo dar un vuelco a la formulación de comprimidos, para lo cual se desarrollará un marco de modelización integrado y mecanicista que prediga los perfiles de disolución con gran precisión. Se prevé que este marco reduzca los errores, acorte el tiempo de desarrollo y mejore la calidad de los medicamentos en Europa.

Objetivo

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.