Formulation of a positively charged testosterone niosome-loaded hydrogel: optimization, IVIVC Correlation, and pharmacokinetic evaluation

The present study deals with the formulation of a hydrogel based on the positively charged niosomes for the delivery of testosterone at an improved skin permeation rate and offering sustained release. Testosterone-loaded niosomes (F1, F2, F3) were prepared with different concentrations of an octadecyl amine as a positive charge inducer combined with Span 60, Tween 60, and cholesterol; subsequently, these were incorporated into a hydrogel matrix of xanthan gum, iota carrageenan, and hyaluronic acid. Characterization confirmed stability, encapsulation efficiency, and diffusion-controlled drug release for each formulation. In vitro, ex vivo, and in vivo pharmacokinetic studies demonstrated that formulation H3, with the highest concentration of octadecyl amine, achieved maximum release and systemic absorption compared to H1, H2, and the marketed Androgel reference. Strong IVIVC correlation supports the potential of niosome-based hydrogel for the transdermal delivery of testosterone and that HF provided an optimized and sustained release of the hormone for clinical applications in hormone replacement therapy.