The use of chemical penetration enhancers (CPEs) is one of the most common approaches to improve the dermal and transdermal delivery of drugs. However, often, incorporation of CPEs in the formulation poses compatibility and stability challenges. Moreover, incorporation of enhancers in the formulation leads to prolonged exposure to skin increasing the concern of causing skin reactions. This study was undertaken to assess whether pretreatment with CPEs is a rational approach to enhance the permeation of diclofenac sodium. In vitro experiments were performed across porcine epidermis pretreated with propylene glycol or oleic acid or their combinations for 0.5, 2, and 4 h, respectively. Pretreatment with combination of oleic acid in propylene glycol was found to enhance the permeation of diclofenac sodium significantly only at 10% and 20% (v/v) level, and only when the pretreatment duration was 0.5 h. Longer durations of pretreatment and higher concentration of oleic acid in propylene glycol did not enhance the permeation of diclofenac sodium. In vivo dermatokinetic studies were carried out on Sprague-Dawley rats. A twofold increase in AUC and Cmax was observed in case of rats pretreated with enhancers over the group that was pretreated with buffer. In conclusion, this study showed that composition of the enhancers and duration of pretreatment are crucial in determining the efficacy of CPEs.
Keywords: formulation; microdialysis; permeability; skin; transdermal.
© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.