The aim of this study was to develop a stable microemulsion (ME) for transdermal delivery of tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA). The lipid-based vehicles were selected by screening cannabinoid solubility and the emulsifying ability of surfactants. Pseudo-ternary phase diagrams were constructed by formulation of cannabinoids with Capryol® 90 as oil phase, Tween® 80, Solutol® HS15, Procetyl® AWS, and Cremophor® RH40 as surfactants, ethanol as cosurfactant, and distilled water as the aqueous phase. A significant improvement in transmembrane flux (Jss), permeability coefficient (Kp), and enhancement ratio (ER) was found in one system compared to other formulations. This ME consisted of 1.0% (w/w) of cannabinoids, 5% (w/w) of Capryol® 90, 44% (w/w) Smix (2:1, Procetyl® AWS and Ethanol) and 50.0% (w/w) of distilled water. Additionally, the effects of pH on the permeation of the cannabinoids were investigated. Based on the pH value THCA and CBDA-loaded ME exhibited the highest permeation at pH 5.17 and pH 5.25. After storing the pH-adjusted P2 ME and the optimized P2 ME for 180 days at 4℃ and 25℃, the content of cannabinoids was over 95%. Consequently, the cannabinoid-loaded ME system is a promising option for solubilizing and stabilizing lipophilic drugs like cannabinoids and utilize them for transdermal delivery.
This research was supported by a grant from the Drug Development Innovation Center and supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1A6A3A03037334). The faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta acknowledges research funding from Xphyto Therapeutics and Applied Pharmaceutical Innovation. We would also like to thank the Cell imaging Facility at the University of Alberta for permitting us to use their instruments.This research was supported by a grant from the Drug Development Innovation Center and supported by Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2020R1A6A3A03037334). The faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta acknowledges research funding from Xphyto Therapeutics and Applied Pharmaceutical Innovation. We would also like to thank the Cell imaging Facility at the University of Alberta for permitting us to use their instruments.
