Gastric floating sustained-release tablet for dihydromyricetin: Development, characterization, and pharmacokinetics study

Abstract

Dihydromyricetin (DHM) is a natural dihydroflavonol compound with quite a number of important pharmacological properties. However, its low solubility in water and poor stability in aqueous environment, have compromised drug efficacy of DHM, thus hindering its clinical use. The present study was to develop DHM-loaded gastric floating sustained-release tablet (DHM-GFT) to improve the bioavailability of DHM. DHM-GFT was prepared via powder direct compression. The formulation of tablet was optimized in terms of the floating ability and drug release rate. The optimized DHM-GFT exhibited short floating lag time of less than 10 s and long floating duration of over 12 h in acidic medium. It had a 12-hour sustained release of DHM, which proved its potential to develop as a twice-a-day dosing preparation. The physicochemical properties of DHM-GFT well satisfied the pharmacopoeial requirements. In addition, the results from pharmacokinetic studies demonstrated that, DHM-GFT could considerably prolong the in vivo residence time of drug and improve the bioavailability via good gastric floating ability and sustained drug release when compared to DHM powder. Therefore, DHM-GFT is promising to promote the application of DHM and merits studies for further development.

Keywords: Bioavailability; Dihydromyricetin; Gastric floating tablet; Pharmacokinetics; Stability; Sustained release.

Fig. 1

The chemical structure of dihydromyricetin (DHM).

Fig. 2

Schematic representation for the preparation of DHM-GFTs.

Fig. 3

The floating abilities of DHM-GFTs with different formulations (F1–F9) as evaluated according to their (A) floating lag time and (B) floating duration in the acidic medium. Data of each formulation were presented as mean ± SD (n = 3).

Fig. 4

The in vitro drug release profiles of DHM-GFTs with the formulations (A) F1, F4, F7 with lower amount of NaHCO₃; (B) F2, F5, F8 with medium amount of NaHCO₃; and (C) F3, F6, F9 with higher amount of NaHCO₃. Data of different time points of each formulation were presented as mean ± SD (n = 3).

Fig. 5

(A) Drug release, (B) swelling, and (C) erosion profiles of the optimized DHM-GFT (formulation F6) in the acidic medium. Data of different time points were presented as mean ± SD (n = 3).

Fig. 6

The plasma concentration-time curves of DHM powder and DHM-GFT at different doses. Data of different time points of each group were presented as mean ± SD (n = 6). Compared to DHM powder, DHM-GFT showed much prolonged drug residence time.