ABSORPTION OF THYROTROPIN-RELEASING-HORMONE IN RATS USING A MUCOADHESIVE BUCCAL PATCH

Mucoadhesive buccal patches were evaluated in vitro and in vivo using rats for release of thyrotropin-releasing hormone (TRH). TRH (10% w/w) was incorporated into mucoadhesive buccal patches that were custom co formulated with silicone and organic polymers (Dow Coming, Midland, MI ) and its release profile was characterized in vitro using a modified Franz diffusion cell. TRH released into pH = 7.0 phosphate buffered sa line at 37 degrees C under sink conditions was detected using high-per formance liquid chromatography (HPLC). Release of nw in vitro from the buccal patches was rapid during the first 2 hr, with 51% of the total amount of TRH incorporated into the patches released after 24 hr. HPL C analysis indicated that TRH extracted from buccal patches thermally stressed at 40 degrees, 55 degrees, and 70 degrees C showed negligible degradation after 6 months. In contrast, an aqueous TRH solution stor ed at 70 degrees C showed degradation of nw as soon as 10 days followi ng incubation at this temperature. TRH patches placed on the buccal mu cosa of anesthetized rats demonstrated rapid stimulation and release o f thyroid-stimulating hormone (TSH) from the anterior pituitary. Thirt y minutes after patch application, plasma concentrations of TSH fluctu ated but remained approximately 4- to 7-fold greater than baseline (pr ior to patch application) TSH concentrations. Therefore, this prelimin ary study has demonstrated that physiologically active TRH was release d from the TRH mucoadhesive buccal patches and systemically absorbed. Thus, the TRH mucoadhesive buccal patches may represent a convenient d elivery system for therapeutic peptides.