Absorption of Thyrotropin-Releasing Hormone in Rats Using a Mucoadhesive Buccal Patch

Abstract

Mucoadhesive buccal patches were evaluated in vitro and in vivo using rats for release of thyrotropin-releasing homne (TRH). TRH (10% w/w) was incorporated into mucoadhesive buccal patches that were custom coformulated 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 saline at 37°C under sink conditions was detected using high-performance liquid chromatography (HPLC). Release of TRH in vitro from the buccal patches was rapid during the first 2 hr, with 51% of the total amount of TRH incolporated into the patches released after 24 hr. HPLC analysis indicated that TRH extracted from buccal patches thermally stressed at 40°, 55°, and 70°C showed negligible degradation after 6 months. In contrast, an aqueous TRH solution stored at 70°C showed degradation of TRH as soon as 10 days following incubation at this temperature. TRH patches placed on the buccal mucosa of anesthetized rats demonstrated rapid stimulation and release of thyroid-stimulating hormone (TSH) from the anterior pituitary. Thirty minutes after patch application, plasma concentrations of TSH fluctuated but remained approximately 4–to 7-fold greater than baseline (prior to patch application) TSH concentrations. Therefore, this preliminary study has demonstrated that physiologically active TRH was released from the TRH mucoadhesive buccal patches and systemically absorbed. Thus, the TRH mucoadhesive buccal patches may represent a convenient delivery system for therapeutic peptides.