Development and Validation of a HPLC Method for Dissolution and Stability Assay of Liquid-Filled Cyclosporine Capsule Drug Products
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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 wordscyclosporine degradation dissolution HPLC liquid-filled capsules
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.
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.
- 2.D. Tedesco, L. Haragsim. Cyclosporine: a review. Journal of Transplantation 2012;230386. 2012.Google Scholar
- 3.Drugs@FDA. 2012.Google Scholar
- 13.Tredger JM. Using cyclosporine neoral immediately after liver transplantation. Therapeutic Drug Monitoring 1995;17Google Scholar
- 14.Bowers LD, Mathews SE. Investigation of the mechanism of peak broadening observed in the high-performance liquid chromatographic analysis of cyclosporine. J Chromatogr A. 1985;333(0):231–8.Google Scholar
- 17.ICH Q2(R1) Validation of analytical procedures: text and methodology;1995.Google Scholar
- 18.Hansch C, Leo A, Hoekman DH. Exploring QSAR. Washington, DC: American Chemical Society;1995Google Scholar