Bioavailability of Δ⁹-tetrahydrocannabinol following intranasal administration of a mucoadhesive gel spray delivery system in conscious rabbits

Background: The purpose of this study was to investigate the potential of the intranasal route for systemic delivery of solubilized Δ⁹- tetrahydrocannabinol (THC). A further aim was to investigate the effect of nasally administered chitosan-based nasal bioadhesive gel on THC bioavailability as a formulation strategy to decrease normal mucociliary drug clearance. Method: The THC formulations were administered intranasally and compared to intravenous administration utilizing conscious rabbits. Results: After nasal administration, the THC nasal solution afforded a Cmax value of 20 ± 3 ng/mL at 20 minutes. Interestingly, the THC loaded in chitosan gel formulation followed almost the same profile at early time points and subsequently afforded a higher Cmax value of 31 ± 4 ng/mL (Tmax = 45 minutes). The absolute bioavailability of THC after nasal delivery was studied to compare plasma THC concentrations after nasal administration with those after intravenous injection. Absolute bioavailability values were 13.3 ± 7.8% and 15.4 ± 6.5% for the THC nasal solution and gel formulations, respectively. Conclusion: The results of the present study suggest that intranasal administration of THC in solution or in a chitosan-based nasal gel formulation could be an attractive modality for delivery of THC systemically.