Use of an 8¹3² Asymmetrical Factorial Design for the In Vitro Evaluation of Ondansetron Permeation Through Human Epidermis

Abstract

The in vitro permeation of ondansetron through human cadaver epidermis, as a preliminary step toward the development of a transdermal therapeutic system, was investigated. In vitro release studies were carried out using modified Franz diffusion cells and human epidermis, taken from cadaver skin by heat separation technique. To estimate the effect of the type and concentration of the penetration enhancers and the skin from different donors, an 8¹3² asymmetrical factorial design was used. Formulations containing lauric acid and oleic acid as penetration enhancers, showed the largest Q values [amounts of ondansetron permeated per unit area of epidermal membrane (µg/cm²)] at 24, 48, and 72 hr, as well as steady‐state flux values, among all formulations tested. The other enhancers increased the flux in the following order: lauryl alcohol > glycerol monooleate > Azone® > cineole > oleyl alcohol > 1‐methyl‐2‐pyrrolidinone. Moreover, the concentration of the penetration enhancer and the type of the skin were proved to significantly affect the permeation rate of ondansetron through human epidermis. From the results obtained, it was shown that the formulations containing lauric acid or oleic acid at 5% or 10% could increase sufficiently the permeation of ondansetron. Therefore, the transdermal administration of ondansetron seems feasible.

Keywords:

• Asymmetrical factorial design
• Ondansetron
• Penetration enhancers
• Transdermal