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.
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Materials
DHM (purity greater than 98%), hydroxypropyl methylcellulose-K4M (HPMC-K4M), hydroxypropyl methylcellulose-K100M (HPMC-K100M), carbomer-971P, sodium bicarbonate (NaHCO3), calcium phosphate dibasic anhydrous (CPDA), sodium chloride, barium sulfate, methanol, acetonitrile, and phosphoric acid were supplied by Shanghai Aladdin Bio-Chem Technology Co., Ltd., China. lipopolysaccharide (LPS) was supplied by Beijing Solarbio Technology Co., Ltd., China.
Ruirui Zhang, Houyin Shi, Sifang Li, Hao Zhang, Dan Zhang, Ailing Wu, Chun Zhang, Chunhong Li, Xiujuan Fu, Siwei Chen, Jiaoyue Shi, Yang Tian, Sihan Wang, Yu Wang, Hao Liu, A double-layered gastric floating tablet for zero-order controlled release of dihydromyricetin: Design, development, and in vitro/in vivo evaluation, International Journal of Pharmaceutics, Volume 638, 2023, 122929, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.122929.
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