Transmucosal Delivery of Oxytocin to Rabbits Using a Mucoadhesive Buccal Patch

Abstract

ABSTRACTA biocompatible, mucoadhesive buccal patch was evaluated in rabbits for transmucosal delivery of peptides. Oxytocin (OT) was incorporated into custom coformulations of Carbopol 974P and silicone polymer and the resulting plasma OT concentration versus time profiles determined following patch application. For comparative purposes, the mean values determined for the elimination half-life (t1/2), volume of distribution (Vd), and the total body clearance (CL) following intravenous injection of OT were 2.9 ± 0.2 min, 85.3 ± 6.7 ml, and 20.4 ± 2.03 ml/min, respectively. Following application of oxytocin-loaded mucoadhesive patches, plasma OT concentrations remained 20- to 28-fold greater from 0.5 to 3.0 hr than control animals administered placebo patches. The steady-state plasma OT concentration (Css) following application of the buccal patches was 80.6 ± 15.9 pg/ml. The lag-time associated with attainment of the Css was 0.45 ± 0.18 hr. Steady-state flux (Jss) of oxytocin in vivo was 139 ± 36.8 ng/hr/cm2. Based on the amount of OT remaining in the patches following removal, the average dose of OT released in vivo was 0.27 ± 0.024 mg with a bioavailability of 0.1%. No significant alterations in mucosal histology were observed when underlying mucosa to which OT patches had been applied were compared to either control (no patch) mucosa or mucosa underneath placebo patches. The mucoadhesive buccal patches were easy to apply and remove, nonirritating to tissue, and able to continuously deliver a nonapeptide over 3 hr. Based on these preliminary studies, the mucoadhesive buccal patches evaluated may represent an improved transmucosal drug delivery system for peptides and conventional drug substances.