In vitro release testing methods for vitamin E nanoemulsions.

This study reports the release properties of the poorly water-soluble active vitamin E acetate from oil/water nanoemulsions containing canola oil, CremophorRH40(®) and Span80(®) prepared using a low energy emulsification method (EPI process). Drug release was measured via dialysis sac and reverse dialysis sac methods as well as USP apparatus 4 fitted with dialysis sac adapters. Macro- and microscopic stability were evaluated and no instabilities were observed during the test period. In vitro release testing was adequately performed using the reverse dialysis sac and USP apparatus 4 methods. However, the dialysis method produced a slower release rate compared to the other methods and this was considered a result of violation of sink conditions within the dialysis sacs as well as inadequate mixing. Micellar solubilization was able to increase vitamin E transport from canola oil to buffer solution, but no model active concentration increase in the nanoemulsion external aqueous phase was observed despite the presence of micelles. Accordingly, it appeared that diffusion across the interfacial film was the rate-limiting step for in vitro release from these nanoemulsions. Sustained/prolonged release of vitamin E was observed and could be explained based on the high partition coefficient and on the nanoemulsion interfacial film proprieties.