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Quantification of Swelling and Erosion in the Controlled Release of a Poorly Water-Soluble Drug Using Synchrotron X-ray Computed Microtomography

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Abstract

The hydration layer plays a key role in the controlled drug release of gel-forming matrix tablets. For poorly water-soluble drugs, matrix erosion is considered as the rate limiting step for drug release. However, few investigations have reported on the quantification of the relative importance of swelling and erosion in the release of poorly soluble drugs, and three-dimensional (3D) structures of the hydration layer are poorly understood. Here, we employed synchrotron radiation X-ray computed microtomography with 9-μm resolution to investigate the hydration dynamics and to quantify the relative importance of swelling and erosion on felodipine release by a statistical model. The 3D structures of the hydration layer were revealed by the reconstructed 3D rendering of tablets. Twenty-three structural parameters related to the volume, the surface area (SA), and the specific surface area (SSA) for the hydration layer and the tablet core were calculated. Three dominating parameters, including SA and SSA of the hydration layer (SA hydration layer and SSA hydration layer ) and SA of the glassy core (SA glassy core ), were identified to establish the statistical model. The significance order of independent variables was SA hydration layer > SSA hydration layer > SA glassy core , which quantitatively indicated that the release of felodipine was dominated by a combination of erosion and swelling. The 3D reconstruction and structural parameter calculation methods in our study, which are not available from conventional methods, are efficient tools to quantify the relative importance of swelling and erosion in the controlled release of poorly soluble drugs from a structural point of view.

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Acknowledgments

We are grateful for the beam time granted from the SSRF Key Program (Z12sr0040) and the financial support from the Ministry of Science and Technology of China (S2010GR0920, 2010ZX09401-402, and 2012ZX09301001-001), the Chinese Academy of Sciences Visiting Professorship for Senior International Scientists (Prof. Peter York) and the National Natural Science Foundation of China (81273453).

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Authors and Affiliations

  1. Center for Drug Delivery Systems, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Xianzhen Yin, Haiyan Li, Zhen Guo, Li Wu, Fangwei Chen & Jiwen Zhang

  2. Anhui University of Traditional Chinese Medicine, Hefei, Anhui, 230038, China

    Li Wu & Jiwen Zhang

  3. Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, China

    Fangwei Chen

  4. Formulation Science, Pharmaceutical Development, AstraZeneca, Macclesfield, UK

    Marcel de Matas

  5. Institute of Pharmaceutical Innovation, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK

    Xianzhen Yin, Qun Shao & Peter York

  6. Shanghai Synchrotron Radiation Facility, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201204, China

    Tiqiao Xiao & You He

Authors
  1. Xianzhen Yin
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  2. Haiyan Li
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  3. Zhen Guo
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  4. Li Wu
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  5. Fangwei Chen
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  6. Marcel de Matas
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  7. Qun Shao
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  8. Tiqiao Xiao
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  9. Peter York
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  10. You He
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  11. Jiwen Zhang
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Corresponding authors

Correspondence to Peter York, You He or Jiwen Zhang.

Additional information

Xianzhen Yin and Haiyan Li contributed equally to this work.

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Yin, X., Li, H., Guo, Z. et al. Quantification of Swelling and Erosion in the Controlled Release of a Poorly Water-Soluble Drug Using Synchrotron X-ray Computed Microtomography. AAPS J 15, 1025–1034 (2013). https://doi.org/10.1208/s12248-013-9498-y

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  • DOI: https://doi.org/10.1208/s12248-013-9498-y

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