Abstract
<title>Abstract</title> <p> Background: Rivastigmine transdermal drug delivery systems (TDDS) provide smoother plasma concentration profiles and improved tolerability compared with oral formulations. Methods: This study aimed to evaluate the bioequivalence, adhesion performance, and safety profile of a branded generic rivastigmine TDDS, Rivazich (13.68 mg, 9.5 mg/24 h) compared with the reference product, Exelon Patch 10 (18 mg, 9.5 mg/24 h) following a single 24-hour application in healthy subjects. In an open-label, randomized, two-period crossover trial conducted under fasting conditions, 74 subjects were enrolled and 58 completed the study. Plasma concentrations of rivastigmine were quantified using a validated HPLC–MS/MS method up to 48 h post-dose. Noncompartmental analysis was performed to derive C <sub>max</sub> , AUC <sub>0–t</sub> , and partial AUCs (0–12 h and 12 h–t) for bioequivalence assessment. Adhesion performance was evaluated at predefined time points, and non-inferiority at 24 h was assessed using a −10% margin, in accordance with regulatory guidance. Results: The 90% confidence intervals for all pharmacokinetic parameters were within the predefined bioequivalence acceptance range of 80–125%. Adhesion analysis demonstrated non-inferiority of the test formulation. Conclusions: According to the regulatory requirements, the test and reference formulations were considered bioequivalent. Trial registration: ClinicalTrials.gov, NCT07464340. Registered 11 March 2026 - Retrospectively registered, https://clinicaltrials.gov/study/NCT07464340 </p>