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Archives of Pharmacal Research

, Volume 30, Issue 8, pp 991–1001 | Cite as

In Vitro andin vivo studies on the complexes of vinpocetine with hydroxypropyl-β-cyclodextrin

  • Shufang Nie
  • Xiaowen Fan
  • Ying Peng
  • Xingang Yang
  • Chao Wang
  • Weisan Pan
Article Drug development

Abstract

The purpose of this study was to evaluate complexes of vinpocetine (VIN), a poorly water-soluble base type drug, with hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous environment and in solid state, with or without citric acid (CA) as an acidifier of the complexation medium. The apparent stability constant (Kc) calculated by phase solubility was 282 M-1 and the complexation in solution was structurally characterized by1H-NMR which showed VIN was likely to fit into the cyclodextrin cavity with its phenyl ring and ethyl ester bond. Solid complexes of VIN and HP-β-CD were prepared by kneading (KE), co-evaporating (CE) and freeze-drying (FD) methods. Physical mixtures were prepared for comparison. The study in the solid state included the differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and infrared absorption spectroscopy (IR). From these analyses, CE and FD products were found in amorphous state, allowing to the conclusion of strong evidences of inclusion complex formation. However, the dissolution test showed that only VIN/HP-β-CD+CA complexes by CE and FD method could provide satisfying dissolution behavior (rapid, complete and lasting) when compared to that of VIN/HP-β-CD complexes. Interestingly, the addition of CA in inclusion complexes could significantly decrease the amount of HP-β-CD needed to solubilize the same amount of VIN and thereby reducing the formulation bulk. Furthermore, in-vivo study revealed that the bioavailability of VIN after oral administration to rabbits (n=6) was significantly improved by VIN/HP-β-CD+CA inclusion complex.

Key words

Vinpocetine Hydroxypropyl-β-cyclodextrin Inclusion complexes Citric acid Improving dissolution rate Bioavailability 

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Copyright information

© The Pharmaceutical Society of Korea 2007

Authors and Affiliations

  • Shufang Nie
    • 1
  • Xiaowen Fan
    • 1
  • Ying Peng
    • 1
  • Xingang Yang
    • 1
  • Chao Wang
    • 1
  • Weisan Pan
    • 1
  1. 1.Department of PharmaceuticsShenyang Pharmaceutical UniversityShenyangChina

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