Development and In vitro Evaluation of Betahistine Adhesive-Type Transdermal Delivery System

Purpose: To develop a transdermal betahistine (BTH) delivery system using different pressure sensitive adhesives (PSAs) including acrylics, polyisobutylene and styrenic rubber solution.
Methods: Formulations were prepared by solvent casting and adhesive transfer method. PSAs acrylate vinylacetate (AVA), hydrophilic acrylate (HA), acrylic non-curing (ANC), polyisobutylene (PIB), and tackified styrenic rubber solution (TSR) -were evaluated for their suitability in terms of miscibility, maximum drug loading, effect on tack property and in vitro permeation through excised guinea pig skin. Furthermore, one of the PSAs was tested in relation to effect of penetration enhancers on tack property, in vitro permeation, in vivo patch adhesion performance and stability.
Results: Only formulations prepared with AVA and HA were stable. Increased drug loading in these PSAs significantly reduced tack. In vitro permeation data across guinea pig skin demonstrated that BTH flux from from the formulation containing HA (F1) was significantly (p < 0.001) higher than that containing AVA (F2). Formulations containing 2 % enhancer showed good tack. Specifically, the formulation containing 2 % oleic acid as enhancer not only showed the highest permeation but also good tack property, non-irritancy for up to 36 h and stability under accelerated conditions.
Conclusion: The formulation containing HA as the PSA and 2 % oleic acid as enhancer demonstrated a good potential for further development to an adhesive-type transdermal delivery system for BTH.

Keywords
Meniere’s syndrome, Transdermal delivery, Betahistine, Pressure-sensitive adhesives, Penetration enhancers