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.


METHODS
The THC formulations were administered intranasally and compared to intravenous administration utilizing conscious rabbits.


RESULTS
After nasal administration, the THC nasal solution afforded a C(max) 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 C(max) value of 31 ± 4 ng/mL (T(max) = 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.


CONCLUSIONS
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.
Department of Pharmaceutical Sciences, University of Kentucky, Lexington, 40536-0082, USA. amalg0@email.uky.edu
Abeer M
AM
Al-Ghananeem
Ahmad H
AH
Malkawi
Peter A
PA
Crooks
D000281:Administration, Intranasal; D058956:Administration, Mucosal; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry*; D013759:Dronabinol / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D008297:Male; D009079:Mucociliary Clearance; D009297:Nasal Mucosa / Q000378:metabolism*; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits
D005079:Excipients; D005782:Gels; D011619:Psychotropic Drugs; D013759:Dronabinol; D048271:Chitosan