Polymorphs and permeability of 3',4'-dimethoxy flavonol-3-O-β-D-glucopyranoside monohydrate

doi:10.5246/jcps.2022.08.053

Abstract

Abstract:

3',4'-Dimethoxy-flavonol-3-O-β-D-glucopyranoside monohydrate (GDH), which can significantly reduce blood lipids, atherosclerotic aortic lesions, and liver injury, has poor oral bioavailability. In the present study, we aimed to prepare and characterize five new polymorphs of GDH (II, III, IV, V, and VI) and the amorphous form of GDH (GDH-AM). The GDH polymorphs and GDH-AM were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). Dissolution tests, physical stability, polymorphic transformation, and permeability studies were subsequently investigated. Dissolution of GDH-II and GDH-IV reached higher concentrations compared with GDH-I. GDH-AM exhibited a significantly high dissolution rate and prolonged supersaturation during dissolution. No phase transition was found for GDH-I and GDH-AM after 3 months of storage, while GDH-II, GDH-III, GDH-IV, GDH-V, and GDH-VI were readily converted to GDH-I. In situ single-pass intestinal perfusion experiments showed that the high concentration of GDH exhibited low permeability. Sodium dodecyl sulfate and bovine bile salts were used as absorption enhancers to improve the permeability of GDH. The results showed that sodium dodecyl sulfate and taurocholate were good absorption enhancers for further formulation development of GDH.

Key words: Polymorph, Amorphous, Solubility, Stability, Permeability

Supporting:

Feng Zhou, Danling Sun, Yiru Wang, Ying Zhang, Yueyi Deng. Polymorphs and permeability of 3',4'-dimethoxy flavonol-3-O-β-D-glucopyranoside monohydrate[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(8): 634-645.

Figures/Tables 11

References 37

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