title: In vitro and in vivo evaluation of a sublingual fentanyl wafer formulation.
abstract: BACKGROUND
  The objective of this study was to prepare a novel fentanyl wafer formulation by a freeze-drying method, and to evaluate its in vitro and in vivo release characteristics, including its bioavailability via the sublingual route.
  
  
  METHODS
  The wafer formulation was prepared by freeze-drying an aqueous dispersion of fentanyl containing sodium carboxymethylcellulose and amylogum as matrix formers. Uniformity of weight, friability, and dissolution testing of the fentanyl wafer was achieved using standard methods, and the residual moisture content was measured. The fentanyl wafer was also examined using scanning electron microscopy and x-ray diffraction. The absolute bioavailability of the fentanyl wafer was evaluated in 11 opioid-naïve adult female patients using a randomized crossover design.
  
  
  RESULTS
  In vitro release showed that almost 90% of the fentanyl dissolved in one minute. In vivo, the first detectable plasma fentanyl concentration was observed after 3.5 minutes and the peak plasma concentration between 61.5 and 67 minutes. The median absolute bioavailability was 53.0%.
  
  
  CONCLUSIONS
  These results indicate that this wafer has potential as an alternative sublingual fentanyl formulation.
authors.affiliation: Pharmacy Department, Armadale Health Service, Armadale, Australia. stephen.lim@health.wa.gov.au
authors.forename: Stephen C B
authors.initials: SC
authors.lastname: Lim
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Paech
authors.forename: Bruce
authors.initials: B
authors.lastname: Sunderland
authors.forename: Yandi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000286:Administration, Sublingual; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D018592:Cross-Over Studies; D005079:Excipients / Q000737:chemistry*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005612:Freeze Drying; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D010865:Pilot Projects; D012995:Solubility; D014961:X-Ray Diffraction; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D005079:Excipients; D002266:Carboxymethylcellulose Sodium; D005283:Fentanyl
keywords: absolute bioavailability; fentanyl wafer; in vitro dissolution; in vivo study; pharmacokinetics; sublingual