Non-Effective Improvement of Absorption for Some Nanoparticle Formulations Explained by Permeability under Non-Sink Conditions

We evaluated the in vitro permeability of nanoparticle formulations of high and low lipophilic compounds under non-sink conditions, wherein compounds are not completely dissolved. The permeability of the highly lipophilic compound, griseofulvin, was improved by about 30% due to nanonization under non-sink conditions. Moreover, this permeability was about 50% higher than that under sink conditions. On the other hand, for the low lipophilic compound, hydrocortisone, there was no difference in permeability between micro-and nano-sized compounds under non-sink conditions. The nanonization of highly lipophilic compounds improves the permeability of the unstirred water layer (UWL), which in turn improves overall permeability. On the other hand, because the rate-limiting step in permeation for the low lipophilic compounds is the diffusion of the compounds in the membrane, the improvement of UWL permeability by nanonization does not improve the overall permeability. Based on this mechanism, nanoparticle formulations are not effective for low lipophilic compounds. To accurately predict the absorption of nanoparticle formulations, it is necessary to consider their permeability under non-sink conditions which reflect in vivo conditions.

Automated summary

This passage mainly discusses the evaluation of the in vitro permeability of high and low lipophilic compound nanoparticle formulations under non-sink conditions. The results show that nanonization can improve the permeability of highly lipophilic compounds, but it does not improve the permeability of low lipophilic compounds. Nanonization improves the overall permeability of highly lipophilic compounds by improving the permeability of the unstirred water layer, while for low lipophilic compounds, nanonization does not improve overall permeability because the rate-limiting step is diffusion in the membrane. Therefore, when predicting the absorption of nanoparticle formulations, it is necessary to consider their permeability under non-sink conditions.