Design, Evaluation, and Activity Testing of Buccal Film Apigenin Nanoemulsion Drug Delivery System as Antidiabetic Agent

Apigenin (4',5,7-trihydroxyflavone) is a flavonoid with antidiabetic potential, but has low water solubility (2.16 μg/L). To overcome this challenge, nanoemulsion formulations were developed to improve apigenin solubility. This research aimed to produce an apigenin nanoemulsion (APG-Ne) that meets quality requirements and can be incorporated into buccal film to facilitate application. Apigenin nanoemulsions (APG-Ne) (F1 – F3) were formed by the self-nanoemulsion method, while buccal film apigenin nanoemulsions (Buccal film APG-Ne) (F1 – F5) were made using the solvent-casting method. All formulations were evaluated for their organoleptic and physicochemical properties. The antidiabetic activity of the formulations was evaluated in vitro by alpha-glucosidase inhibitory assay, and in vivo using alloxan-induced diabetic rabbits. APG-Ne met the requirements for self-nanoemulsion with globule size of < 29.74 nm, polydispersity index (PDI) < 0.9766, pH 6.21 - 6.20, and zeta potential close to 0 mV. The best formula was F3 APG-Ne with significantly improved solubility 34 times higher than that of pure apigenin. All buccal film APG-Ne formulations met the quality criteria, with F5 showing the highest percentage drug release (71.06 ± 0.08% and 0.1879 ± 0.07 g/film sheet). APG-Ne (F3) and buccal film APG-Ne (F5) exhibited potent antidiabetic activity by significantly inhibiting α-glucosidase enzyme (IC50 = 55.23 ppm, and 48.03 ppm, respectively), and lowering blood glucose in alloxan-induced diabetic rabbits, producing a 66 ± 11.14 mg/dL decrease in blood glucose after seven days of treatment. Therefore, buccal film APG-NE is an innovative drug delivery system with improved solubility and bioavailability of apigenin as potential antidiabetic agent.