Design and in vitro evaluation of capsaicin transdermal controlled release cubic phase gels

Abstract

The purpose of this study was to design and investigate the transdermal controlled release cubic phase gels containing capsaicin using glycerol monooleate (MO), propylene glycol (1,2-propanediol, PG), and water. Three types of cubic phase gels were designed based on the ternary phase diagram of the MO-PG-water system, and their internal structures were confirmed by polarizing light microscopy (PLM) and small-angle X-ray scattering (SAXS). Release results showed the cubic phase gels could provide a sustained system for capsaicin, while the initial water content in the gels was the major factor affecting the release rate. Release kinetics was determined to fit Higuchi's square-root equation indicating that the release was under diffusion control. The calculated diffusion exponent showed the release from cubic phase gels was anomalous transport. The unique structure of the cubic phases, capsaicin distributed in the lipid bilayers, and cubic phase gel swelling contributed to the release mechanism. The cubic phase gel may be an interesting application for transdermal delivery system of capsaicin in alleviating the post-incision pain.

Fig. 1

Ternary phase diagram for the MO–PG–water system at room temperature. The dots represent samples prepared. B two-phase region, Lα lamellar phase, C cubic phase

Fig. 2

Polarized photomicrographs of Lamellar phase (a, b) and cubic phase (c) at room temperature (magnification ×400). a MO–PG–water (90–0–10). b MO–PG–water (21–49–30). c MO-PG-water(63-7-30)

Fig. 3

SAXS diffraction patterns obtained from the three chosen cubic phase samples

Fig. 4

Plots of the reciprocal d-spacings (q) as a function of the Miller indices, (h ² + k ² + l ²)^1/2, from the observed reflections in the SAXS diffraction patterns for the cubic phase gels

Fig. 5

Cumulative capsaicin released from cubic phase gels versus time

Fig. 6

Scheme of cubic phases’ structure illustrating the mechanism for capsaicin release from the cubic phases (Adapted with modifications from Refs (14, 20))