Synergistic iontophoretic drug delivery of risedronate sodium in combination with electroporation and chemical penetration enhancer: In‐vitro and in‐vivo evaluation

Abstract

In the present investigation iontophoretic permeation of risedronate sodium (RS) through optimized gel based formulation
was evaluated with respect to various electrical parameters like Current density and type of current. The study also
involved enhancement the iontophoretic permeation of RS in combination with electroporation and chemical penetration enhancers with its inâ€vivo Pharmacokinetic evaluation.The permeation studies were carried through the human cadaver skin
by using modified Franz diffusion cell and microcontroller based devices for iontophoresis and electroporation developed in the laboratory. Inâ€vivo Pharmacokinetic studies were carried out in hairless rats. One way ANOVA followed by Tukeyâ€Kramer test for multiple comparisons. The permeation of RS was significantly increased with iontophoresis at 0.5 mA/Cm2 current density.The iontophoretic permeation was found depend on current density and ON:OFF ratio.The pulsatile current resulted in high permeation than continuous current. Maximum permeation was obtained at 0.5 mA/cm2 with 1:1 pulsed current. When iontophoresis was coupled with chemical penetration enhancers and electroporation for 100 ms at 220V, synergistic enhancement in permeation was observed with shortened lag time and high flux. The required flux was achieved with area of application 1.55 cm2. Inâ€vivo studies in hairless rats revealed high Cmax, low tmax and increased area under the curve with electroporation, followed by iontophoresis indicated increased bioavailability. Relative bioâ€availability was 4.6 when calculated in comparison to passive studies.

Key words: Electroporation, iontophoresis, penetration enhancers, risedronate sodium