title: Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers.
abstract: BACKGROUND
  The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and 'breakthrough' pain that may occur in certain conditions like cancer. To fulfill this goal, suitable noninvasive drug delivery systems need to be developed for CBD. Chronic pain relief can be best achieved through the transdermal route, whereas 'breakthrough' pain can be best alleviated with intranasal (IN) delivery. Combining IN and transdermal delivery for CBD may serve to provide patient needs-driven treatment in the form of a nonaddictive nonopioid therapy.
  
  
  OBJECTIVE
  Herein we have evaluated the IN and transdermal delivery of CBD with and without permeation enhancers.
  
  
  METHODS
  In vivo studies in rats and guinea pigs were carried out to assess nasal and transdermal permeation, respectively.
  
  
  RESULTS
  CBD was absorbed intranasally within 10 minutes with a bioavailability of 34-46%, except with 100% polyethylene glycol formulation in rats. Bioavailability did not improve with enhancers. The steady-state plasma concentration of CBD in guinea pigs after transdermal gel application was 6.3 +/- 2.1 ng/mL, which was attained at 15.5 +/- 11.7 hours. The achievement of a significant steady-state plasma concentration indicates that CBD is useful for chronic pain treatment through this route of administration. The steady-state concentration increased by 3.7-fold in the presence of enhancer. A good in vitro and in vivo correlation existed for transdermal studies.
  
  
  CONCLUSIONS
  The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
authors.forename: Kalpana S
authors.initials: KS
authors.lastname: Paudel
authors.forename: Dana C
authors.initials: DC
authors.lastname: Hammell
authors.forename: Remigius U
authors.initials: RU
authors.lastname: Agu
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Valiveti
authors.forename: Audra L
authors.initials: AL
authors.lastname: Stinchcomb
mesh_terms: D000042:Absorption; D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002185:Cannabidiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002186:Cannabinoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006168:Guinea Pigs; D008297:Male; D010539:Permeability / Q000187:drug effects; D051381:Rats; D054772:Rats, Hairless; D012867:Skin
chemical_list: D000700:Analgesics; D002186:Cannabinoids; D005079:Excipients; D002185:Cannabidiol