Summary

Dissolution is a crucial process in the effect of orally inhaled drugs, because the time it takes for the dissolution of a drug particle will influence the time the drug will be available for uptake. Predictive and discriminating in vitro methods are needed in order to ascertain and assess this dissolution profiles. Currently, no tests for inhaled products have reached compendial status but several approaches are being studied. These methods mostly consist of a donor and an acceptor compartment, and a membrane that separates them. A model was developed by May et al. (Pharm. Res. 31, 3211–3224, 2014) to describe experimentally obtained dissolution data for inhaled particles, however diffusion across the membrane was not taken into account in this model. Therefore, the aim of this study was to develop a mechanistic model that would account not only for dissolution but also for diffusion across the membrane. Such a model was formulated using the simplified description of drug dissolution obtained by the Noyes–Whitney equation coupled to diffusional release across the membrane, inferred from Fick’s law. In conclusion, a mechanistic model was developed that could analyse membrane-type in vitro dissolution set ups. The developed model could successfully describe the release profiles of previously published dissolution data and can be used to establish rate-controlling mechanisms. The model provides information about the amount of solid that was left in the donor compartment and the amount of drug that was released into the acceptor compartment.

Key Message

In this study, a mechanistic model was developed that can be used to analyse membrane-type in vitro dissolution set ups by taking into account not only dissolution but also diffusion across the membrane, thus providing information about the relative importance of the rate-controlling mechanisms