Influence of Inclusion Complexation and Skin Microporation on Enhancement of Transdermal Permeation of Raloxifene Hydrochloride

Abstract

The aim of the present investigation was to develop an inclusion complex-based hydrogel for transdermal delivery of raloxifene hydrochloride. Inclusion complexation was tried using two types of cyclodextrins, β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Kneading, co-precipitation, solvent evaporation and freeze drying were the methods explored for preparing inclusion complexs. The prepared complexes were characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray powder diffraction and both in vitro and ex vivo drug release studies. Kneading method was found to be the most suitable for preparing the inclusion complexes. Phase solubility studies indicated that β-cyclodextrin gave rise to Bs type of curve while hydroxypropyl-β-cyclodextrin resulted in Ap type of curve. The stability constants (K1:1) obtained for β-cyclodextrin and hydroxypropyl-β-cyclodextrin were 1572 and 2960, respectively. Complexation efficiency of hydroxypropyl-β-cyclodextrin was higher than that of β-cyclodextrin. Differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray powder diffraction studies indicated the superiority of hydroxypropyl-β-cyclodextrin for complexing raloxifene hydrochloride. In vitro and ex vivo studies showed that highest drug release occurred from inclusion complex prepared with hydroxypropyl-β-cyclodextrin with a ratio of 1:2.5. Histopathology studies revealed that the developed hydrogel was non-irritant and micropores were clearly visible for the microporated skin.