Introduction: Oral transmucosal delivery of fentanyl is a rapid and proven route of administration for breakthrough pain in cancer patients^1,2. However, variability in fentanyl pharmacokinetics has been observed with the use of Actiq^®, which is attributed to several uncontrolled factors including patient mouth surface area, patient diligence in the application process, and the amount of swallowed fentanyl³. BEMA^TM Fentanyl consists of a small, bilayered, water erodible polymer unit that adheres to the oral mucosa and rapidly delivers fentanyl into the systemic circulation through a defined surface area.

Methods: A total of 12 healthy volunteers received single 800µg doses of three BEMA^TM fentanyl citrate formulations (pH 6.0, 7.25, 8.5) and Actiq^® 800µg at 48 hour intervals in an open-label, four-period, Latin-square, crossover study. Serial blood samples for fentanyl analysis were collected over a 48-hour period after each dose.

Results: Plasma fentanyl concentrations were greater and were observed earlier with all three formulations of BEMA^TM Fentanyl than with Actiq^®, with the pH 7.25 formulation having the best profile. Compared to Actiq^®, peak plasma fentanyl concentrations with BEMA^TM Fentanyl pH 7.25 occurred earlier (median T_max 1.0 vs. 2.0 hr and mean T_first 9.0 vs. 13.2 min) and were significantly higher (mean C_max 1.67 vs. 1.03ng/mL, p<0.05). Overall exposure was also greater with BEMA^TM Fentanyl than with Actiq^® (mean AUC_inf 14.5 vs. 10.3hr·ng/mL). The BEMA^TM Fentanyl units adhered to the oral mucosa within 5 seconds of application and dissolved in less than 30 minutes without irritation.

Conclusion: All three BEMA^TM Fentanyl formulations provided faster absorption, higher maximum plasma concentrations, and greater systemic exposure to fentanyl compared to Actiq^®, while BEMA^TM Fentanyl pH 7.25 offered the best profile.