Background: The oral bioavailability of Raloxifene hydrochloride, an
FDA approved selective estrogen receptor modulator, is severely limited due to its
poor aqueous solubility and extensive first pass metabolism. The Present work focuses
on the development of ethosomal hydrogel for transdermal delivery of
Raloxifene HCl as an alternate way to solve aforementioned problem. The physical
breaching of stratum corneum, the principal barrier, by microneedle treatment was
also employed to potentiate its transdermal permeation.
Methods: The influence of lipid and ethanol concentration on vesicle size and entrapment
efficiency was extensively investigated using response surface methodology
based on central composite design. The software based optimization was done
and validated using check point analysis. Optimized batch was extensively evaluated for its safety, efficacy
Results: The optimized ethosomal batch possessed 403 nm size and 74.25% drug entrapment. Its zeta
potential and in vitro drug release were also found favorable for transdermal permeation. The ex vivo
skin permeation study revealed a transdermal flux of 4.621 μg/cm2/h through the intact pig ear skin
which was further enhanced through the microporated skin (transdermal flux, 6.194 μg/cm2/h) with a
3.87 fold rise when compared to drug permeation from plain solution applied over intact skin (transdermal
flux, 1.6 μg/cm2/h). Histopathological skin sections showed the non-irritant nature of the ethosomal
hydrogel and microneedle treatment. The formulation was found stable under both refrigeration
and room temperature conditions for 6 weeks.
Conclusion: In a nutshell, the developed system was found efficient, safe and stable and seems promising
for transdermal use.