A Double-layered Gastric Floating Tablet for Zero-order Controlled Release of Dihydromyricetin: Design, Development, and in Vitro/in Vivo Evaluation

Dihydromyricetin (DHM) is an important natural flavonoid. However, most of DHM preparations have shown shortcomings such as low drug loading, poor drug stability, and/or large fluctuations in blood concentration. This study aimed to develop a gastric floating tablet with a double-layered structure for zero-order controlled release of DHM (DHM@GF-DLT). The final product DHM@GF-DLT showed a high average cumulative drug release at 24 h that best fit the zero-order model, and had a good floating ability in the stomach of the rabbit with a gastric retention time of over 24 h. The FTIR, DSC, and XRPD analyses indicated the good compatibility among the drug and the excipients in DHM@GF-DLT. The pharmacokinetic study revealed that DHM@GF-DLT could prolong the retention time of DHM, reduce the fluctuation of blood drug concentration, and enhance the bioavailability of DHM. The pharmacodynamic studies demonstrated that DHM@GF-DLT had a potent and long-term therapeutic effect on systemic inflammation in rabbits. Therefore, DHM@GF-DLT had the potential to serve as a promising anti-inflammatory agent and may develop into a once-a-day preparation, which was favorable to maintain a steady blood drug concentration and a long-term drug efficacy. Our research provided a promising development strategy for DHM and other natural products with a similar structure to DHM for improving their bioavailability and therapeutic effect.