Abstract

Purpose:To investigate the effect of various vehicles and skin permeation enhancers on the in vitro skin permeation and in vivo skin absorption of ondansetron hydrochloride (OND) and to investigate the possible mechanism of this enhancement. Method: OND solutions were prepared by dissolving OND in isopropyl alcohol or propylene glycol and various permeation enhancers. Skin permeation of OND was determined through the skin excised from Yucatan micropigs (YMP) using the in vitro Franz–type diffusion cells. OND solutions were applied to rabbit skin and OND plasma concentrations were determined by HPLC. The X-ray diffraction (XRD) measurements of stratum corneum were carried out. The XRD experiments were performed at BL40B2 of the SPring-8. Results: The in vitro skin permeability of OND was enhanced by using fatty acids and terpenes with 40% isopropyl alcohol as solubilizer. A higher degree of skin permeation was observed using oleic acid in the presence of propylene glycol in place of 40% isopropyl alcohol. Maximum OND skin permeation was obtained with a solution including oleic acid and propylene glycol, each at a level 5 times that of OND. In vivo absorption of the drug from a solution including oleic acid and propylene glycol continued to increase from 30 min of administration up to at least 6 h after administration. The XRD profile of the stratum corneum was changed by treatment with propylene glycol, and oleic acid. Conclusion: It is suggested that the combination of propylene glycol and oleic acid as vehicles is effective in promoting the skin permeation of OND, and the possible mechanism of this enhancement is related to disorder of the membrane structure of the stratum corneum.


Keywords:  Skin permeation   Oleic acid   Propylene glycol   Solubility   Ondansetron   XRD