Mathematical modelling of drug release from porous granules #

Kevin Moroney, Michael Vynnycky

10:30 Tuesday in 3Q68.

Part of the Mathematical medicine session.

Abstract #

In vitro dissolution testing is an important step in the development of pharmaceutical oral solid dosage forms, such as tablets and capsules. In the development of new drug formulations, these tests are used to gain an understanding of the mechanisms and rate of drug release over time. However, the observed release profile may arise from a complex interplay of several processes, including tablet disintegration into granules, granule de-aggregation into drug and filler particles, and dissolution of individual drug particles. Meanwhile, drug leaching from the tablet and granule may occur while they remain intact. The ability to mathematically model these processes accurately, individually and collectively, is important to understand how the formulation parameters can be adjusted to control the release. In this talk, a model describing one pathway of drug release from a porous drug-excipient granule or population of granules is presented. The model explicitly accounts for drug solubility limitations and microstructural variations within the granule(s) that are commonly neglected. The model is analysed in certain limits of practical interest leading to the analysis and solution of a moving boundary value problem. The model is compared to experimental data and model limitations and extensions are discussed.