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Synthesis
DOI: 10.1055/s-0043-1775476
paper

Quality by Design Driven Improved Process of Abiraterone Acetate

Sasikala Cheemalapati Venkata Annapurna
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
b   Department of Chemistry, GITAM University, Rudraram, Hyderabad - 502329, Telangana, India
,
Srinivas Talasila Rao
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Pavan Kumar Bathini 
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Prashanth Reddy Gaddameedhi
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Shravan Kumar Komati
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Amarendhar Manda
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Pradip D. Nahide
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
B Ramalinga Reddy
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Mukesh Kumar Madhra
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
,
Ratnamala Annapragada∗
b   Department of Chemistry, GITAM University, Rudraram, Hyderabad - 502329, Telangana, India
,
Rakeshwar Bandichhor∗
a   Dr. Reddy’s Laboratories Ltd., Integrated Product Development, Innovation Plaza, Bachupally, Hyderabad - 500090, Telangana, India
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Abstract

Abiraterone is an antiandrogen and selective inhibitor of 17α-hydroxylase/C17,20-lyase (CYP17) and is currently used in the treatment of metastatic castration-resistant prostate cancer and metastatic high-risk castration-sensitive prostate cancer. Here an improved kilogram scale synthesis of Abiraterone is presented, starting from commercially available dehydroepiandrosterone (DHEA) by employing Quality by Design (QbD) principles, statistical design of experiments (DoE), and green metrics parameters to evaluate the environmental impact and efficiency. This article focuses on identifying critical quality attributes (CQAs), exploring the relationship between CQAs and material attributes (MAs), and determining the critical process parameters (CPPs) for synthesizing hydrazone, vinyl iodide intermediates, and the final product, Abiraterone acetate. The presented approach effectively managed critical impurities and achieved impressive yields of 98, 84, and 78% with purity >99% in the hydrazone, vinyl iodide intermediate, and final API, respectively. The improved synthesis was optimized and scaled for multi-kilogram batches, addressing challenges from previous methods and yielding ICH quality material in 65% overall yield.

Key words

design of experiments - quality by design - green chemistry - abiraterone acetate - dehydroepiandrosterone

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1775476.
  • Supporting Information


Publication History

Received: 19 February 2025

Accepted after revision: 26 March 2025

Article published online:
28 April 2025

© 2025. Thieme. All rights reserved

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