Design Space Visualization and Technoeconomic Evaluation of a Batch Manufacturing Process for the Green Production of an Anti-cancer Drug (Adavosertib) Precursor
Matthew Blair, Mazaher Molaei Chalchooghi, Robert J. Cox and Dimitrios I. Gerogiorgis*,
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引用次数: 0
Abstract
The development of cost-effective and sustainable manufacturing processes is a growing priority in the pharmaceutical industry, with many companies turning to computational modeling to reduce reliance on experimental campaigns. Established simulation frameworks must however support in silico pharma R&D, especially for detailed process design and optimization. This paper introduces a robust but simple and flebible modeling framework for simulating and optimizing batch manufacturing processes, applying it to the production of AZD1775 HMS (a small-molecule intermediate required for the synthesis of the experimental anti-cancer drug Adavosertib). The entire design space is mapped using high-fidelity submodels for batch reactors and liquid–liquid extraction (LLE) units. The impact of solvent selection, reagent concentration, separation solvent ratio, operating temperature, and equipment size on process viability has also been evaluated, towards identification of a cost-optimal and environmentally friendly LLE solvent system (water–acetonitrile–toluene) and process conditions. Drug development can thus be streamlined by this systematic pathway for sustainable manufacturing, achieving economic and environmental goals simultaneously.
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.
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