Effects of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin Inclusions on the Degradation of Magnolol by Intestinal Bacteria

Abstract

Cyclodextrin (CD) inclusions are generally used to increase the solubility of poorly soluble drugs. In this study, magnolol (MAG) was used as a model drug for exploring the effects of CD on the degradation of pharmaceutical drugs by intestinal microflora. MAG/β-cyclodextrin (β-CD) and MAG/hydroxypropyl-β-CD (HP-β-CD) inclusion complexes were successfully prepared by the saturated aqueous solution and freeze-drying methods, respectively. Structural characterisation along with analyses of solubility, residual water content and drug content of the inclusion complexes was performed. The intestinal microflora of male rats was used to study MAG degradation in vitro. At three concentrations, the degradation of both the inclusion complexes was slower than that of the MAG monomer, MAG and CD mixtures and the MAG-poloxamer 188 micelle. There were no statistically significant differences in the degradation of the MAG/β-CD and MAG/HP-β-CD inclusion complexes. A simulation first-order equation of the degradation parameters revealed that the degradation of the inclusion complexes was slower and pronounced, judging by slope. The experimental findings were verified by molecular docking for predicting the stable molecular structure of the inclusion complexes. In conclusion, the inclusion complexes partially protected MAG from degradation by the intestinal bacteria.

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Abbreviations

CD:

Cyclodextrin (Fw=~1135, purity ≧98%)

MAG:

Magnolol

MAG/β-CD:

MAG/β-cyclodextrin

MAG/HP-β-CD:

MAG/hydroxypropyl-β-cyclodextrin (DS = 6.1, Fw = 1489, purity ≥ 91%)

RSD:

Relative standard deviation

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Correspondence to Weiguang Shan or Zhenhai Zhang.

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The Laboratory Animal Welfare Ethics Committee of Zhejiang University of Technology approved the animal experiments.

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We studied the effects of β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusion on the degradation of MAG by intestinal bacteria. The degradation of both the inclusions was slower than that of the MAG monomer, MAG and CD mixtures and micelle which demonstrated that the inclusion had a protective effect on the degradation of intestinal flora.

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Tang, L., Zhu, Z., Xie, M. et al. Effects of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin Inclusions on the Degradation of Magnolol by Intestinal Bacteria. AAPS PharmSciTech 20, 244 (2019). https://doi.org/10.1208/s12249-019-1397-9

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KEY WORDS

  • intestinal flora
  • magnolol
  • inclusion complex
  • degradation