Glimepiride (GMD) is a hypoglycemic agent that has variation in bioavailability for its unexpected absorption. Glimepiride was formulated in a buccal film loaded with a nanobased formulation to enhance its absorption via buccal mucosa. Nanostructured lipid carriers (NLCs) and d-α-tocopherol polyethylene glycol 1000 succinate-based micelles enhance GMD solubility and improve its permeation through the buccal mucosa. The formulation variables were optimized using a Box-Behnken design. These factors, such as the percent of micelles relative to NLC ( X 1), the percent of Carbopol ( X 2), and the percent of permeation enhancer ( X 3), were investigated for their effect on the initial release ( Y 1) and the cumulative release after 6 hours ( Y 2). The optimum levels for X 1, X 2, and X 3 were 100%, 0.05%, and 1.8%, respectively. The optimized formulation revealed that the permeation of GMD from the film was in favor of micelles. This optimized film was then coated with ethyl cellulose to direct the release only through the buccal mucosa. The optimized unidirectional GMD transmucosal film showed a release of 93.9% of GMD content at 6 hours compared to 60.41% of GMD release from the raw GMD film. This finding confirmed the suitability of transmucosal delivery of GMD via the buccal mucosa.
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