Development of a novel cannabinoid-loaded microemulsion towards an improved stability and transdermal delivery

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 (R) 90 as oil phase, Tween (R) 80, Solutol (R) HS15, Procetyl (R) AWS, and Cremophor (R) 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 (R) 90, 44% (w/w) Smix (2:1, Procetyl (R) 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 pHadjusted P2 ME and the optimized P2 ME for 180 days at 4 degrees C and 25 degrees C, 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.