Obtaining the substance enoxaparin sodium equivalent to the original Clexane® and Lovenox®. Selection of technological parameters of the key stage of the synthesis

Authors

DOI:

https://doi.org/10.15587/2519-4852.2023.277735

Keywords:

Enoxaparin, Low molecular weight heparin, technological parameters, compositional analysis, HSQC, size-exclusion chromatography, reducing, non-reducing ends

Abstract

The aim: to carry out the key stage of synthesis to obtain a substance equivalent to the original drugs Clexane® and Lovenox® by determining the technological parameters of the synthesis that are critical from the point of view of the formation of the molecule and studying the correlation between the structural characteristics of Enoxaparin samples and the experimental conditions of the technological process.

Materials and methods: samples of the Enoxaparin sodium substance were synthesized according to the method described in the patent, as well as with a variation of the selected critical technological parameters. The obtained samples of Enoxaparin sodium were analyzed according to pharmacopoeial requirements, as well as by non-pharmacopoeial methods, such as two-dimensional NMR spectroscopy and size exclusion chromatography for detailed structural characterization of the molecule.

Results: determination and variation of technological parameters critical for the formation of the molecule, such as temperature, the amount of alkali for the depolymerization reaction, and the reaction time of the reaction mass, were determined and varied. Enoxaparin sodium samples were developed according to the selected parameters and a detailed analysis of the structure of the obtained samples was carried out, followed by a comparison with the original Clexane® and Lovenox®. It was established that with an increase in the temperature of the reaction mass, the amount of alkali and the holding time individually and in combination, the degree of depolymerization increases, which makes the composition of the molecule unbalanced in comparison with the original drugs Clexane® and Lovenox®.

Conclusions: As a result of the experiments, the technological parameters of the synthesis of a sample of Enoxaparin sodium were evaluated and determined, allowing to obtain a substance comparable to the originator in terms of chemical structure (alkali/ heparin benzyl ester ratio 0.06; temperature – 57 °C, reaction mixture holding time - 1.5 hours)

Supporting Agency

  • JSC Farmak

Author Biographies

Yuliia Bovsunovska, JSC Farmak; National University of Pharmacy

Engineer-Technologist of Bioorganic Synthesis

Postgraduate Student

Department of Pharmaceutical Chemistry

Vitalii Rudiuk, JSC Farmak

Head of Laboratory

API Synthesis Laboratory

Volodymyr Mishchenko, National University of Pharmacy

PhD, Associate Professor

Department of Pharmaceutical Technologies and Medicines Quality Assurance

Institute for Advanced Training of Pharmacy Specialists

Victoriya Georgiyants, National University of Pharmacy

Doctor of Pharmacy, Professor, Head of Department

Department of Pharmaceutical Chemistry

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Obtaining the substance enoxaparin sodium equivalent to the original Clexane® and Lovenox®. Selection of technological parameters of the key stage of the synthesis

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Published

2023-04-30

How to Cite

Bovsunovska, Y., Rudiuk, V., Mishchenko, V., & Georgiyants, V. (2023). Obtaining the substance enoxaparin sodium equivalent to the original Clexane® and Lovenox®. Selection of technological parameters of the key stage of the synthesis. ScienceRise: Pharmaceutical Science, (2(42), 46–56. https://doi.org/10.15587/2519-4852.2023.277735

Issue

No. 2(42) (2023)

Section

Pharmaceutical Science

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Copyright (c) 2023 Yuliia Bovsunovska, Vitalii Rudiuk, Volodymyr Mishchenko, Victoriya Georgiyants

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