AAPS PharmSciTech

, Volume 14, Issue 1, pp 10–18

Molecular Modeling-Based Inclusion Mechanism and Stability Studies of Doxycycline and Hydroxypropyl-β-Cyclodextrin Complex for Ophthalmic Delivery

  • Haohao Zhang
  • Meiwan Chen
  • Zixin He
  • Zhouhua Wang
  • Meimei Zhang
  • Zhouyang He
  • Qian Wan
  • Dan Liang
  • Michael A. Repka
  • Chuanbin Wu
Research Article

DOI: 10.1208/s12249-012-9877-1

Cite this article as:
Zhang, H., Chen, M., He, Z. et al. AAPS PharmSciTech (2013) 14: 10. doi:10.1208/s12249-012-9877-1

Abstract

The aim of the present study was to prepare a stable complex of doxycycline (Doxy) and hydroxypropyl-β-cyclodextrin (HPβCD) for ophthalmic delivery and investigate the inclusion mechanism and the inclusion effects on the stability of Doxy. The Doxy/HPβCD complex was prepared by solution stirring and then characterized by scanning electron microscopy and ultraviolet spectroscopy. Based on results of nuclear magnetic resonance, molecular model of Doxy/HPβCD complex was established using computational simulation of PM3 method implemented in Gaussian 03. Stabilities of Doxy/HPβCD complex in both aqueous solution and solid state at 25°C were evaluated by HPLC. Finally, in vitro antibacterial activity of the Doxy/HPβCD complex was evaluated by disk diffusion test. It was found that the stabilities of Doxy/HPβCD complex in both aqueous solution and solid state were improved obviously as compared with Doxy alone. This stability enhancement is consistent with the inclusion mechanism between HPβCD and Doxy, which showed that the unstable site of Doxy molecule at 6-CH3 was protected in the hydrophobic cavity of HPβCD, additionally, the chelation of Mg2+ provided a synergetic protection of the other unstable site of Doxy at 4-N(CH3)2. The antibacterial activity results indicated that Doxy/HPβCD complex might have potential for clinical applications.

KEY WORDS

doxycyclinehydroxypropyl-β-cyclodextrininclusion mechanismmolecular modelingstability

Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Haohao Zhang
    • 1
  • Meiwan Chen
    • 2
  • Zixin He
    • 1
  • Zhouhua Wang
    • 1
  • Meimei Zhang
    • 1
  • Zhouyang He
    • 1
  • Qian Wan
    • 3
  • Dan Liang
    • 3
  • Michael A. Repka
    • 4
  • Chuanbin Wu
    • 1
  1. 1.School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouPeople’s Republic of China
  2. 2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical SciencesUniversity of MacauMacaoPeople’s Republic of China
  3. 3.State Key Laboratory of OphthalmologyZhongshan Ophthalmic Center, Sun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  4. 4.Department of Pharmaceutics, School of PharmacyThe University of MississippiOxfordUSA