Targeted transdermal scopolamine delivery over the salivary glands for sialorrhea: Dose-response and systemic safety in rats.

Sialorrhea is a common and distressing symptom in patients with neurological disorders, often impairing quality of life and increasing the risk of aspiration. Although oral anticholinergic agents are widely prescribed, their systemic side effects frequently limit long-term adherence. This study investigated the dose-response relationship and systemic safety of transdermal scopolamine applied directly over the salivary glands in a rat model. Formulations containing 0.2%, 0.5%, 1%, and 5% scopolamine (0.05 g per rat) were compared with oral administration at a dose of 0.2 mg/kg. Transdermal application resulted in a dose-dependent reduction in salivary volume, with the 1% formulation demonstrating greater and more sustained suppression than that observed with oral administration. Lower formulation concentrations (0.2% and 1%) did not significantly affect fecal output or tear secretion, whereas the 5% formulation and oral administration caused significant reductions in both. Plasma scopolamine levels increased with higher scopolamine concentrations in the transdermal formulation, whereas oral administration resulted in higher but more variable systemic exposure. These findings suggest that targeted transdermal delivery to the salivary glands may offer localized efficacy, reduced systemic exposure, and improved tolerability. The targeted transdermal approach may provide a safer and more adjustable strategy for managing sialorrhea, warranting further clinical investigations.