Controlled release of testosterone by polymer-polymer interaction enriched organogel as a novel transdermal drug delivery system: Effect of limonene/PG and carbon-chain length on drug permeability

Abstract The aim of this research is to develop a transdermal drug delivery system (TDDS) for testosterone by novel physical chain entanglement organogels in propylene glycol. The organogels have been widely studied for TDDS, due to their good interactive properties with skin. The physical gel with amphiphilic polymers was studied and evaluated in this study, in order to fabricate the controllable release and sufficient permeability through the skin barrier of transdermal testosterone. The novel sugar amine-derived gel, that is poly(vinyl benzyl-N-methyl-D-glucamine) gel (poly(VbNMDG) gel), was obtained by the subsequent polymerization of the neutral form (VbNMDG) and cationic form (VbNMDG-H) with an organic base as a promotor. The gel showed electrostatic interactions as indicated by FTIR, and responsive behavior under alkali conditions. The network structure is generated from multi-interaction of linear polymer chain, confirmed by in situ polymerization. This was evidenced by the rheological measurement, which confirmed a gradual change from sol to gel-like behavior. Regarding the drug release, we set the target release time at 24 h, which is an effective treatment condition for hypogonadism. For the permeation, it was studied by using abdominal rat skin as a membrane. The d -limonene/PG synergistic activity enhanced the permeability, resulting in the highest coefficient (KD/L) at 8.80 ± 1.95 cm/h at 10% Limonene/PG. Furthermore, we evaluated the carbon chain length effect by copolymerizing of benzalkonium chloride. The dodecyl (C-12) group showed significant penetration enhancement, indicated by the coefficient which was 13.76 ± 5.45 cm/h.