Efficient Process Development of Abiraterone Acetate by Employing Design of Experiments

Area of Science:

• Pharmaceutical Chemistry
• Process Chemistry
• Drug Synthesis

Background:

• Abiraterone acetate is a crucial drug for prostate cancer treatment.
• Efficient and high-purity synthesis is essential for pharmaceutical manufacturing.
• Existing synthesis routes may face challenges with impurity control and yield.

Purpose of the Study:

• To develop an efficient synthesis process for abiraterone acetate.
• To apply Quality by Design (QbD) principles and statistical Design of Experiments (DoE).
• To identify and control critical quality attributes (CQAs), material attributes (MAs), and critical process parameters (CPPs).

Main Methods:

• Implementation of Quality by Design (QbD) principles.
• Statistical Design of Experiments (DoE) for process optimization.
• Risk assessment to identify critical factors in hydrazone, vinyl iodide, and final API synthesis.

Main Results:

• Successful control of critical impurities: deacylated, 17-methyl, hydroxy, and diene impurities.
• Achieved high selectivity (95%, 85%, 82%) and purity (99%, 96%, 99%) for intermediates and final API.
• Significantly improved process throughput from 25% to 57% through DoE-identified parameter optimization.

Conclusions:

• The QbD and DoE approach enables efficient and robust synthesis of abiraterone acetate.
• This optimized process enhances product quality by minimizing critical impurities.
• The developed methodology offers a scalable and improved manufacturing process for abiraterone acetate.