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An improved and robust scale-up process aided with identification and control of critical process impurities in darunavir ethanolate

  • Sathyanarayana Girigani
  • Harnam SinghEmail author
  • Sankar Rao Kola
  • Vijayalaxmi Dayanand Yelmeli
  • Venu Gopal Regula
  • Sakshi Shah
  • Neelu Jain
  • Pramod KumarEmail author
Article
  • 8 Downloads

Abstract

A robust and safe industrial process, including five isolations and drying steps for widely prescribed anti-HIV (protease inhibitor) drug darunavir ethanolate 2, has been developed. A salient feature of this process is the development of procedures enabling the efficient synthesis of multi-kilogram quantity of darunavir ethanolate, and process demonstrations through plant scale preparation are offered where darunavir molecule has been prepared with overall > 70% chemical yield and > 99.8% purity without involving any purification procedure(s), with all possible process impurities below than the desired limit (not more than 0.08%) were isolated, synthesized and characterized. The developed process is entirely robust, very efficient and demonstrated up to kilograms scale.

Keywords

Darunavir Safe industrial process Reduction Deprotection Coupling Critical process impurities 

Notes

Acknowledgements

The authors greatly appreciate financial support for this work from Micro Labs Ltd., API Division Centre, ML-27, Bangalore. We thank our group colleagues for their appreciated contribution. The Analytical Department of Micro Labs Limited acknowledged for providing support for analytical and spectral data.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflict of interest.

Supplementary material

11164_2019_3948_MOESM1_ESM.pdf (1.8 mb)
Supplementary material 1 (PDF 1848 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Sathyanarayana Girigani
    • 1
    • 2
  • Harnam Singh
    • 1
    Email author
  • Sankar Rao Kola
    • 1
  • Vijayalaxmi Dayanand Yelmeli
    • 1
  • Venu Gopal Regula
    • 1
  • Sakshi Shah
    • 1
  • Neelu Jain
    • 2
  • Pramod Kumar
    • 1
    Email author
  1. 1.Chemical Research and Development, API R&D CentreMicro Labs Ltd.BangaloreIndia
  2. 2.Sri Satya Sai University of Technology and Medical SciencesSehoreIndia

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