Enhanced permeation parameters of optimized nanostructured simvastatin transdermal films: ex vivo and in vivo evaluation.

OBJECTIVE

Detailed optimization process was carried out to enhance permeation parameters, and hence bioavailability, of simvastatin (SMV) transdermal films.

METHODS

SMV solubility was investigated in various oils, surfactants and co-surfactants/co-solvents. Mixtures of the selected components were prepared to identify zone of nanoemulsion formation that was utilized in Extreme Vertices mixture design to develop SMV self-nanoemulsifying drug delivery systems (SNEDDS) with minimum globule size. Optimized SMV-SNEDDS were included in the preparation of transdermal films. A fractional factorial design was implemented to evaluate effects of the factors on the amount of SMV permeated. The optimized film was investigated for ex vivo skin permeation and in vivo pharmacokinetic parameters.

RESULTS

The optimum SNEDDS formula was 0.09, 0.8 and 0.11 for Sefsol 218, tween 80 and PEG 200, respectively. Fractional factorial design depicted the optimized SMV transdermal film with 2% HPMC and 2% DMSO as permeation enhancer that showed 1.82-fold improvements in skin flux. The pharmacokinetic data showed higher C and almost doubled AUC compared with raw SMV-loaded films.

CONCLUSION

The two-step optimization implemented to optimize and control the experimental conditions for the preparation of SMV-SNEDDS-transdermal film with improved ex vivo skin permeation and enhanced in vivo parameters.