Effects of vehicles on the percutaneous absorption of donepezil hydrochloride across the excised hairless mouse skin

Objectives: This study aimed to examine the feasibility of developing donepezil transdermal delivery systems (TDSs). Methods: Solution and pressure-sensitive adhesive (PSA) TDS were formulated using various vehicles and fatty acids, and the in vitro permeation study was conducted using the hairless mouse skin. Key findings: Permeation fluxes (μg/cm ²/h) from solution formulations were generally low (0.053.40), except for formulations including isopropyl alcohol (IPA, 51.19), ethyl alcohol (27.32) and water (24.07). Dose-dependent permeation fluxes were obtained (r ² = 0.9754). Even though the addition of fatty acids to IPA failed to increase donepezil permeation rates, it shortened lag times. Compared to those from solution formulations, permeation profiles from PSA TDS were totally different, and penetration rates were considerably low. PSA TDS comprising diethylene glycol monoethyl ether (DGME)-propylene glycol monolaurate (PGML) co-solvents (40:60) showed the highest permeation flux (0.10 ± 0.0024 μg/cm ²/h). Conclusions: IPA-containing solution formulations and DGME-PGML (40: 60)-containing PSA TDS were found to be favorable candidates for donepezil transdermal delivery.