Enhancement of transdermal permeation of cannabinoids and their pharmacodynamic evaluation in rats

The objective of the present study was to enhance the transdermal permeation of cannabinoids: cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV) using chemical permeation enhancer approach and evaluate them for their anti-inflammatory effect in vivo in a paw edema model in rats. Cannabinoids gel formulations were developed using FDA approved inactive ingredients: lactic acid (LA), polyethylene glycol-400 (PEG-400), N-methyl-2 pyrrolidone (NMP), dimethyl sulfoxide (DMSO). In vitro skin permeation testing (IVPT) showed flux of ∼13.25 μg/cm²/h for CBD, ∼9.38 μg/cm²/h for CBG and ∼51.74 μg/cm²/h for THCV. Additionally, IVPT study showed cumulative drug permeation of 610.96 ± 88.92 μg/cm², 432.09 ± 35.59 μg/cm² and 2384.44 ± 42.22 μg/cm² from CBD, CBG and THCV gel formulations respectively. Further, effect of excipients on cannabinoid permeation showed that, formulation containing lactic acid, NMP and DMSO showed significantly (p<0.0001) enhanced flux of cannabinoids as compared to formulation without LA, NMP and DMSO. In vivo studies showed that paw edema was significantly (p<0.0001) reduced in the groups containing CBD, CBG, THCV as compared to control and placebo formulation. In conclusion, flux of CBD, CBG and THCV was significantly enhanced using chemical permeation enhancers approach which helped in reducing rat paw edema.