CONTROLLED BUCCAL DELIVERY OF BUPRENORPHINE

Buprenorphine is a potent opiate agonist-antagonist used in the treatment of both acute and chronic pain. Like many opiates, it has low oral bioavailability due to both presystemic metabolism in the wall of the gastrointestinal tract and extensive first pass metabolism. Controlled delivery of analgesics results in good pain relief and a lower total requirement for the drug. Buccal delivery offers advantages in terms of accessibility, avoidance of first pass metabolism and the ability to provide controlled delivery for extended periods of time. Buccal permeation of buprenorphine was measured in vitro and in vivo in the dog model using prototype non-woven and hydrogel systems. The fluxes of drug were identical from solutions and from non-woven systems in vitro, providing a reliable way of applying a drug solution to the mucosa without leaking. A model is described that permits screening of potential buccal systems in vitro to select a system for in vivo use. In vivo, steady-state plasma levels were obtained using both non-woven and hydrogel systems. Steady state was attained in 1 to 1.5 h and was maintained during the time of application of the system. Assuming that the flux in man is similar to that in the dog, controlled buccal delivery of buprenorphine would provide adequate analgesia over an extended period of time.