ORAL-MUCOSA CONTROLLED DELIVERY OF LHRH BY BILAYER MUCOADHESIVE POLYMER SYSTEMS

Several mucoadhesive devices have been developed from mucoadhesive pol ymers for the enhanced and controlled transmucosal delivery of LHRH th rough oral mucosa. The mucoadhesive devices developed are of a bilayer type, which consist of a fast-release layer containing PVP (k-30), an d a sustained-release layer formulated from Carbopol 934 and PVP (k-90 ). They have been designed for a prolonged application onto the gingiv al/alveolar mucosa for a period of up to 24 h. These oral mucosa LHRH delivery devices also contain enhancer, sodium cholate, to promote the transmucosal permeation of LHRH and stabilizer, cetylpyridinium chlor ide, to stabilize LHRH from degradation by the microflora. In order to simulate the in vivo condition, a specially designed device holder wa s also used to have one side of the mucoadhesive device adhering to th e alveolar mucosa and the other side facing the buccal mucosa. Results from the release kinetics studies demonstrated a burst release of LHR H from the fast-release layer, which provide a rapid delivery of LHRH, and a prolonged release of LHRH from the sustained-release layer, whi ch maintains a sustained delivery of LHRH. Permeation kinetics studies indicated that the transmucosal permeation of LHRH increases as incre asing the loading dose of either LHRH or enhancer in the fast-release layer, but decreases as increasing the ratio of Carbopol 934/PVP (k-90 ) in the sustained-release layer. The formulation of the mucoadhesive device can be varied to achieve a specific rate of transmucosal permea tion.