Scalable Process Development of Ceritinib: Application of Statistical Design of Experiments

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-12-17 DOI:10.1021/acs.oprd.4c00416

Shravan Kumar Komati, Amarendhar Manda, Sridhar Vasam, Gopal Chandru Senadi, Arthanareeswari Maruthapillai, Rakeshwar Bandichhor

引用次数: 0

Abstract

A convenient and commercially viable cost-effective, safe manufacturing process was developed to manufacture ceritinib. This work describes the implementation of the quality by design approach through the identification of critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs). Application of the statistical design of experimentation for an experimental plan to find the relationship between CQAs, CMAs, and CPPs. This work also describes a superior process for large-scale manufacturing of ceritinib in terms of process safety, handling, scalability, and enhanced throughput. Work captured here addressed the challenges in reported procedures such as sodium hydride’s explosive hazard, high-temperature microwave conditions, nitro to amine reduction under high pressure using a palladium catalyst, and column chromatography to purify the finished product.

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为生产塞瑞替尼开发出了一种方便且具有商业可行性的经济、安全生产工艺。这项工作介绍了通过确定关键质量属性（CQA）、关键材料属性（CMA）和关键工艺参数（CPP）来实施质量设计方法。在实验计划中应用实验统计设计，找出 CQA、CMA 和 CPP 之间的关系。这项工作还从工艺安全性、处理、可扩展性和提高产量等方面描述了大规模生产塞瑞替尼的卓越工艺。这里的工作解决了已报道程序中的难题，如氢化钠的爆炸危险、高温微波条件、使用钯催化剂在高压下将硝基还原为胺，以及柱色谱法纯化成品。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.