Gastric floating pill enhances the bioavailability and drug efficacy of dihydromyricetin in vivo

Abstract Dihydromyricetin (DHM) is a natural flavonol compound that has shown significant pharmacological activities such as anti-atherosclerosis, anti-diabetes, anti-oxidation, and anti-inflammation, but its clinical application has been hindered by its poor stability and rapid metabolism that reduced its bioavailability in vivo. Since DHM is more stable under acidic conditions, selective and sustained absorption of DHM in the stomach via gastric floating drug carriers provide an attractive way to settle the problems. Previously, we reported a gastric floating tablet for DHM that demonstrated improved stability and bioavailability of the drug. However, the application of this drug carrier was still constrained by low drug content percentage, and short floating and drug releasing durations. Besides, the influences of dosage forms on the drug efficacy of DHM in vivo were not yet clear. In this study, gastric floating pill as a novel sustained-release dosage form for DHM (DHM-GFP) was developed using combined techniques of extrusion molding and freeze drying. The physicochemical properties of DHM-GFP could well meet the pharmacopoeial requirements for pills. Our data indicated that DHM-GFP had significantly higher drug content percentage, improved floating ability and more sustained drug release than the previously reported DHM tablet, and is promising to become a once-a-day dosing preparation. More importantly, this novel dosage form resulted in notably prolonged residence time, improved bioavailability, and enhanced anti-inflammatory effect of DHM in vivo, indicating its great potential to translate this natural compound into clinical application.