Research of irinotecan stability in different methods of active loading into liposomes

Authors

  • Александр Викторович Стадниченко National Technical University «Kharkiv Politechnical Institute» Bagaliya str., 21, Kharkiv, Ukraine, 61002, Ukraine
  • Юрий Михайлович Краснопольский National Technical Univercity «Kharkiv Politechnical Institute» Bagaliya str., 21, Kharkiv, Ukraine, 61002, Ukraine
  • Виталий Иванович Швец Moscow State Univercity of fine chemical technologies, name of М. V. Lomonosov Vernadskogo ave., 86, Moscow, Russia, 119571, Ukraine
  • Татьяна Григорьевна Ярных National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002, Ukraine

DOI:

https://doi.org/10.15587/2519-4852.2016.74454

Keywords:

liposomes, Irinotecan, impurities formation, “pH gradient” technology, “ammonium gradient” technology, HPLC

Abstract

Irinotecan active encapsulation mechanisms into liposomes according “pH gradient” and “ammonium gradient” technologies were considered.

Aim. Research of Irinotecan stability at typical for each “chemical gradient” technology pH values, and estimation of the impurities content correspondence with Draft quality control methods on " Related impurities” index, using Irinotecan conversion mechanism data.

Methods. HPLC method was used for research, using Shimadzu LC-20 appliance, according to the USP impurities control method for semisynthetic product.

Results. Impurity formation dynamics, similar to Irinotecane E lactone ring destruction product, was studied in 3 stages: at pH values 1.9, 5.0, and 5.5. Impurities formation wasn’t observed at pH 1.9, and Irinotecan was stable during observation period – within 12 hours. At pH 5.0, Irinotecan was stable during 12 hours, while impurities formation in quantity over specifications for the finished product was not observed. At pH 5.5, which is specific for the “ammonium gradient” technology, impurities formation was observed in one hour, which is more than 3 times exceeds permissible norms for impurities content in Liposomal Irinotecan finished dosage form.

Conclusion. It has been found, that in terms of active compound stability, “pH gradient” technology is preferred compared to the “ammonium gradient” technology. After using “pH gradient” technology, “Related impurities” index corresponded to the Draft quality control methods. The obtained data were used for Irinotecan liposomal dosage form development for the further preclinical and clinical study

Author Biographies

Александр Викторович Стадниченко, National Technical University «Kharkiv Politechnical Institute» Bagaliya str., 21, Kharkiv, Ukraine, 61002

Candidate of pharmaceutical sciences

Department of Biotechnology, Biophisics and Analytical Chemistry

Юрий Михайлович Краснопольский, National Technical Univercity «Kharkiv Politechnical Institute» Bagaliya str., 21, Kharkiv, Ukraine, 61002

Doctor of pharmaceutical sciences, professor

Department of «Biotechnology, Biophisics and Analytical Chemistry»

Виталий Иванович Швец, Moscow State Univercity of fine chemical technologies, name of М. V. Lomonosov Vernadskogo ave., 86, Moscow, Russia, 119571

Doctor of chemical sciences, professor, Academic RASc

Department of Biotechnology and nanobiotechnology

Татьяна Григорьевна Ярных, National University of Pharmacy Pushkinska str., 53, Kharkiv, Ukraine, 61002

Doctor of pharmaceutical sciences, professor, Honored person of Science and Technology of Ukraine

Department of drug technology

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Published

2016-08-31

How to Cite

Стадниченко, А. В., Краснопольский, Ю. М., Швец, В. И., & Ярных, Т. Г. (2016). Research of irinotecan stability in different methods of active loading into liposomes. ScienceRise: Pharmaceutical Science, (2 (2), 30–35. https://doi.org/10.15587/2519-4852.2016.74454

Issue

Section

Pharmaceutical Science