Optimization of self-nanoemulsifying systems for the enhancement of in vivo hypoglycemic efficacy of glimepiride transdermal patches

Abstract

Objectives: To optimize and use of glimepiride (GMD)-loaded self-nanoemulsifying delivery systems (SNEDs) for the preparation of transdermal patches.

Methods: Mixture design was utilized to optimize GMD-loaded SNEDs in acidic and aqueous pH media. Optimized GMD-loaded SNEDs were used in the preparation of chitosan (acidic) and hydroxypropyl methyl cellulose (HPMC) (aqueous) films. The prepared optimized formulations were investigated for ex vivo skin permeation, for in vivo hypoglycemic activity and for their pharmacokinetic parameters using animal model.

Results: The optimized formulations showed flux value of (2.88 and 4.428 μg/cm(2)/h) through rat skin for chitosan and HPMC films, respectively. The pattern of GMD release from both formulations was in favor of Higuchi and approaching zero order models. The n values for Korsmeyer-Peppas equation were characteristic of anomalous (non-Fickian) release mechanism. Moreover, HPMC patches have shown significant reductions (p < 0.05) in blood glucose levels; (213.33 ± 15.19) mg/100 ml from the base-line measurement after 12 h of application.

Conclusions: Optimized GMD SNEDs patches were found to improve GMD skin permeability and the essential pharmacokinetic parameters. Further extensive pre/clinical studies are necessary prior to use transdermal GMD as a valuable alternative to peroral dosage forms with improved bioavailability, longer duration of action and more patient convenience.

Keywords: chitosan; glimepiride; hydroxypropyl methyl cellulose; mixture design; self-nanoemulsifying delivery systems; transdermal film.