Transdermal Delivery of Physostigmine: Effects of Enhancers and Pressure-Sensitive Adhesives

ABSTRACT The purpose of this study was to investigate the effects of various pressure- sensitive adhesives (PSA) on the percutaneous absorption of physostigmine across hairless mouse skin. In addition, the influences of various vehicles and polyvinylpyrrolidone (PVP) on the percutaneous absorption of physostigmine from PSA matrix across hairless mouse skin were evaluated using a flow-through diffusion cell system at 37°C. Physostigmine showed the highest permeability from silicone adhesive matrix, followed by polyisobutylene (PIB), styrene– isoprene–styrene (SIS), acrylic, and styrene–butadiene–styrene (SBS) matrix. Among acrylic adhesives, the permeability of physostigmine was the highest from grafted acrylic adhesive. Polyvinyl pyrrolidone inhibited the crystallization of physostigmine in the PIB adhesive matrix and enhanced the permeability of physostigmine from the PIB adhesive matrix. When esters of sorbitol and fatty acid, polyethylene glycol (PEG) alkyl esters, and caprylic/capric triglycerides were tested, the more lipophilic was a surfactant, the higher the permeation rate within the same group of surfactants. The enhancement effect of PEG derivatives was lower than that of non-PEG derivatives. Among non-linear fatty acid derivatives, linoleate derivatives showed higher permeability of physostigmine than oleate derivatives. This study showed that several non-ionic surfactants, including PEG-20 evening primrose glyceride, enhanced the permeation of physostigmine across hairless mouse skin better than oleic acid.