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AAPS PharmSciTech

, Volume 14, Issue 3, pp 959–967 | Cite as

Development and Validation of a HPLC Method for Dissolution and Stability Assay of Liquid-Filled Cyclosporine Capsule Drug Products

  • Xiaoming Xu
  • Abhay Gupta
  • Patrick Faustino
  • Pradeep M. Sathe
  • Vilayat A. Sayeed
  • Mansoor A. Khan
Research Article

Abstract

To assay the dissolution samples of a drug product from several sources, a simple but broadly applicable analytical method is always desired. For the liquid-filled cyclosporine capsules, while analyzing the dissolution samples, the current compendial and literature HPLC methods have been found to be inadequate to provide satisfactory separation of the drug and the excipient peaks. Accordingly, a suitable isocratic reverse-phase HPLC method was developed for the analysis of dissolution samples of liquid-filled cyclosporine capsules. The method successfully separated the cyclosporine peak from the interfering chromatographic peaks of the excipients. The method was validated according to the ICH and FDA guidelines. Specificity, selectivity, linearity, accuracy, precision, and robustness were established over 3 days as part of method validation. Additionally, the degradation kinetics of cyclosporine in dissolution media was determined. Cyclosporine degradation followed a zero-order kinetics in the dissolution media with the respective rate constants of −3.5, −1.5, and −0.3%/h at 37°C, 25°C, and 10°C.

Key words

cyclosporine degradation dissolution HPLC liquid-filled capsules 

Notes

Acknowledgments

This project was funded by regulatory science and review enhancement (RSR) funding from FDA, and was supported in part by an appointment to the ORISE Research Participation Program at the CDER administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and CDER.

Disclaimer

The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Xiaoming Xu
    • 1
  • Abhay Gupta
    • 1
  • Patrick Faustino
    • 1
  • Pradeep M. Sathe
    • 2
  • Vilayat A. Sayeed
    • 2
  • Mansoor A. Khan
    • 1
  1. 1.Division of Product Quality Research, OTR/OPSFood and Drug AdministrationSilver SpringUSA
  2. 2.Office of Generic Drugs, OPSRockvilleUSA

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