Predicting surfactant effects on drug permeation across hollow fiber membrane

The hollow fiber membrane (HFM) system is a potential combined dissolution/permeation in vitro tool to predict oral solid dosage form performance. However, drug permeability interpretation in the presence of surfactants remains mechanistically challenging, particularly when surfactants are present in both the donor and receiver compartments. A model denoted the reduced resistance model was recently employed to explain enhanced drug permeability when surfactant was present in the receiver. The objective was to re-examine previously published HFM flux of griseofulvin and meloxicam to consider the reduced resistance model as an additional contributing mechanism impacting drug flux. Published HFM data under all four surfactant experimental scenarios (i.e., no surfactant, surfactant in the receiver only, surfactant in the donor only, and surfactant in both donor and receiver) were re-analyzed. For the latter two most complex scenarios, there were six competing permeation models. For these two scenarios, the best predictive model for griseofulvin was the reduced resistance model for total donor drug concentration; meanwhile, for meloxicam, which was much less micelle incorporated, the best predictive model was the simple free drug permeation model. Overall, these findings demonstrate that drug permeation across HFM in surfactant-containing systems is governed by the interplay between donor-side micellar sequestration and receiver-side resistance reduction.