Transdermal Delivery of Baclofen Using Iontophoresis and Microneedles.

Abstract

Baclofen, a GABAb agonist, is used in the treatment of multiple sclerosis, a neurodegenerative disease. Currently available dosage forms to deliver baclofen are through the oral and the intrathecal routes. The disadvantage of oral baclofen is that it requires administering the drug multiple times a day, owing to baclofen's short half-life. On the other hand, intrathecal baclofen pumps are invasive and cannot be an alternative to oral baclofen. Hence, there is a need to develop a dosage form that can deliver baclofen non-invasively and for an extended period at a steady rate, increasing the dosing interval. A transdermal baclofen delivery system might be the solution to this problem. Hence, this research focuses on evaluating microneedles, iontophoresis, and a combination of microneedles-iontophoresis as transdermal delivery enhancement strategies for baclofen. In vitro permeation studies were conducted on dermatomed porcine ear skin using vertical Franz diffusion cells to evaluate transdermal baclofen delivery. Anodal iontophoresis was applied at a current density of 0.5 mA/cm2, and transdermal delivery was assessed from pH 4.5 (45.51±0.76 μg/cm2) and pH 7.4 (68.84±10.13 μg/cm2) baclofen solutions. Iontophoresis enhanced baclofen delivery but failed to reach target delivery. Maltose microneedles were used to create hydrophilic microchannels on the skin, and this technique enhanced baclofen delivery by 89-fold. Both microneedles (447.88±68.06 μg/cm2) and combination of microneedles - iontophoresis (428.56±84.33 μg/cm2) reached the target delivery range (222-1184 μg/cm2) for baclofen. The findings of this research suggest that skin could be a viable route for delivery of baclofen. Graphical Abstract.