Transbuccal peptide delivery: stability and in vitro permeation studies onendomorphin-1

The purpose of this study was to investigate the feasibility of buccal deli very of a model peptide, endomorphin-1 (ENI), using stability and in vitro permeation studies. ENI is a recently isolated mu -opiate receptor agonist with high selectivity and specificity for this receptor subtype. Stability studies were conducted in various buffers and the drug was shown to be stab le in both acidic and basic buffer systems. In the presence of full thickne ss porcine buccal epithelium, ENI was unstable with only 23.4 +/- 15.7% int act drug present after 6 h. The region responsible for this degradation was found to coincide with the major barrier region of the buccal epithelium a s delineated through stability experiments in the presence of partial thick ness buccal epithelium. Various peptidase inhibitors were used to isolate t he enzyme(s) responsible for this degradation. Diprotin-A, a potent inhibit or of dipeptidyl peptidase IV, provided significant inhibition of the degra dation of ENI in the presence of buccal epithelium. In vitro permeation stu dies revealed that the permeability coefficient of ENI across porcine bucca l epithelium was 5.67 +/- 4.74 x 10(-7) cm/s. The enzymatic degradation of ENI was found not to be rate limiting to the drug's permeation across bucca l epithelium, as diprotin-A did not increase the permeation of ENI. Sodium glycocholate as well as sodium taurocholate were also ineffective in enhanc ing the permeation of ENI across porcine buccal epithelium. (C) 2001 Publis hed by Elsevier Science B.V.