SUSTAINED ORAL MUCOSAL DELIVERY IN HUMAN VOLUNTEERS OF BUPRENORPHINE FROM A THIN NON-ERODING MUCOADHESIVE POLYMERIC DISK

The feasibility of sustained controlled delivery of pharmacologically relevant amounts of the opiate analgesic buprenorphine from a novel, m ucoadhesive non-eroding oral mucosal patch was assessed in human volun teers. In a randomized, two-period crossover study, each subject recei ved a 0.5 cm(2) patch containing 2.9 mg of buprenorphine free base at one of two oral mucosal sites (upper gum or upper lip) in period 1 of the study and at the alternate site in period 2. Patches were removed after 12 h of wear and residual drug in the patch was measured. Serum buprenorphine concentrations from time of patch application through 24 h post-application were determined. Measurements of pupillary miosis, an indicator of opiate pharmacologic activity, were made at intervals over each 24-h study period. Safety, comfort and mucoadhesion were as sessed. No serious safety problems were encountered; adverse experienc es were mild to moderate and were consistent with the known effects of buprenorphine. Irritation to the oral mucosa was low and acceptable. Comfort and taste were acceptable. Patches adhered satisfactorily for the entire 12-h wear period when applied to the gum, but adhesion to t he lip site was less satisfactory. After an initial lag time of about 1-3 h, pharmacologically relevant serum concentrations of buprenorphin e, as assessed by pupillary miosis, were attained and generally sustai ned for 12-24 h post-dose. Changes in pupillary diameter correlated we ll with serum buprenorphine levels. Serum buprenorphine AUCs after gum and lip application of the patches were 5594 +/- 1419 and 3958 +/- 78 0 pg h/ml, respectively, and indicated greater delivery of buprenorphi ne from the patches applied to the gum versus the lip, possibly due to the superior mucoadhesion at the gum site.