Development and in vitro evaluation of pressure sensitive adhesive patch for the transdermal delivery of galantamine: Effect of penetration enhancers and crystallization inhibition

Abstract

The transdermal route offers an attractive alternative route of drug administration especially for Alzheimer’s disease patients through eliminating gastrointestinal side effects and ultimately improving compliance. In this study, we prepared an optimized matrix–type patches for the transdermal delivery of galantamine free base with ex vivo and in vitro evaluation. Four pressure sensitive adhesives with different functional groups, ten penetration enhancers and four drug loadings were tested to determine the optimized patch. The ex vivo permeation of the different formulated patches through human cadaver skin using vertical Franz diffusion cells showed that GELVA GMS 788 was the best pressure sensitive adhesive among the tested polymers. FT-IR and rheological studies done to investigate any potential interactions of the polymer with the drug and/or additives showed the possibility of hydrogen bonding between the drug and pressure sensitive adhesive (PSA), also the additives had a plasticization effect causing increased flexibility of the polymer chains. The optimized formulation had 10%w/w drug loading, 5% w/w limonene as a penetration enhancer, and 5%w/w oleic acid as a crystallization inhibitor. The combination of limonene and oleic acid increased the flux of galantamine by 2.7-fold compared to 1.7-fold when limonene was used alone. The optimized patch exhibited diffusion release kinetics and fitted well to Higuchi’s model and yielded a permeation rate of 32.4 ± 1.41 µg/cm2/h across human cadaver skin.