We demonstrate that the release of a poorly soluble molecule from nanoporous carriers is a complex process that undergoes heterogeneous surface nucleation events even under significantly diluted release conditions, and that those events heavily affect the dynamics of release. Using beta-carotene and porous silicon as loaded molecule and carrier model, respectively, we show that the cargo easily nucleates at the pore surface during the release, forming micro- to macroscopic solid particles at the pores surface. These particles dissolve at a much slower pace, compared to the rate of dissolution of pure beta-carotene in the same solvent, and they negatively affect the reproducibility of the release experiments, possibly because their solubility depends on their size distribution. We propose to exploit this aspect to use release kinetics as a better alternative to the induction time method, and to thereby detect heterogenous nucleation during release experiments. In fact, release dynamics provide much higher sensitivity and reproducibility as they average over the entire sample surface instead of depending on statistical analysis over a small area to find clusters.
Keywords: carotene; drug delivery; heterogeneous nucleation; nanopores; porous silicon.