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Journal of Pharmaceutical Innovation

, Volume 11, Issue 2, pp 109–119 | Cite as

Influence of Soluplus on Solid-State Properties and Physical Stability of Indomethacin-Saccharin Co-crystal Formation Prepared by Air-Drying Process

  • Shan-Yang LinEmail author
  • Hong-Liang Lin
  • Ying-Ting Chi
  • Ru-Ying Hung
  • Yu-Ting Huang
  • Wei-Hsien Hsieh
  • Chi-Yu Kao
Original Article

Abstract

Purpose

The effect of Soluplus on the solid-state characteristics and physical transformation of indomethacin (IMC), saccharin (SAC), IMC-SAC physical mixture, and the previously prepared IMC-SAC co-crystal was investigated after solvent evaporation via air-drying process.

Methods

Soluplus with γ-IMC or SAC (weight ratio = 1:1) was respectively prepared by completely dissolving both components in acetone by ultrasonication, and then evaporated via air-drying process. Soluplus was fully co-dissolved with the previously prepared IMC-SAC co-crystal (procedure I) or completely dissolved together with IMC-SAC physical mixture (procedure II) in acetone by ultrasonication, and then evaporated through air-drying process. The physical stability of both Soluplus/IMC-SAC systems was also carried out under accelerated storage conditions. All the samples were determined by thermoanalytical and FTIR spectroscopic studies with spectral curve-fitting technique.

Results

Soluplus caused the amorphous formation of IMC or SAC in the Soluplus solid dispersion, in which the intermolecular hydrogen bonding interaction between SAC and Soluplus occurred. Although Soluplus did not influence the co-crystal formation between IMC and SAC in the solid dispersion, the polymorphic transformation and physical stability of Soluplus/IMC-SAC solid dispersion were markedly influenced by procedures I and II after evaporation via air-drying process.

Conclusion

Soluplus influences the amorphous or crystalline IMC-SAC co-crystal formulated in the solid dispersion prepared by procedure I or II via air-drying process. The amorphous IMC-SAC co-crystal in the Soluplus solid dispersion prepared by procedure I gradually transformed to a crystalline IMC-SAC co-crystal after storage at 40 ± 2 °C/75 ± 5 % RH conditions for 28 days, whereas the crystalline IMC-SAC co-crystal in the Soluplus solid dispersion prepared by procedure II via air-drying process maintained a long-term storage stability.

Keywords

Soluplus Indomethacin (IMC) Saccharin (SAC) Solid dispersion Co-crystal Stability Amorphous Crystalline Storage 

Notes

Acknowledgments

This work was supported by Ministry of Science and Technology, Taipei, Taiwan, ROC (MOST 103-2320-B-264-002-MY2).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no competing financial interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Shan-Yang Lin
    • 1
    Email author
  • Hong-Liang Lin
    • 1
  • Ying-Ting Chi
    • 1
  • Ru-Ying Hung
    • 1
  • Yu-Ting Huang
    • 1
  • Wei-Hsien Hsieh
    • 1
  • Chi-Yu Kao
    • 1
  1. 1.Department of Biotechnology and Pharmaceutical TechnologyYuanpei University of Medical TechnologyHsin ChuRepublic of China

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