Sustained oral mucosal delivery in human volunteers of buprenorphine from a thin non-eroding mucoadhesive polymeric disk

Abstract The feasibility of sustained controlled delivery of pharmacologically relevant amounts of the opiate analgesic buprenorphine from a novel, mucoadhesive non-eroding oral mucosal patch was assessed in human volunteers. In a randomized, two-period crossover study, each subject received 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 assessed. No serious safety problems were encountered; adverse experiences 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 the lip site was less satisfactory. After an initial lag time of about 1–3 h, pharmacologically relevant serum concentrations of buprenorphine, as assessed by pupillary miosis, were attained and generally sustained for 12–24 h post-dose. Changes in pupillary diameter correlated well with serum buprenorphine levels. Serum buprenorphine AUCs after gum and lip application of the patches were 5594 ± 1419 and 3958 ±780 pg · h / ml , respectively, and indicated greater delivery of buprenorphine from the patches applied to the gum versus the lip, possibly due to the superior mucoadhesion at the gum site.