Computer aided solvent design to minimise solvent use in integrated synthesis, purification & isolation for sustainable pharmaceutical manufacturing

这可能令人惊讶，但就每公斤产品产生的废物而言，制药行业比炼油行业糟糕1000倍左右；该行业每生产一公斤产品产生约100公斤有害废物，其中大部分是溶剂。拟议的“SolvIT”竞标将建立在Strathclyde和帝国理工学院在建模和溶剂设计领域的现有合作基础上，同时与新的合作伙伴加强团队合作，以解决这一巨大的浪费问题。我们的愿景是提高新药品和现有药品的生产效率，减少浪费，降低成本，使其生产更加可持续和环保。我们计划通过三个主要的工作方案来做到这一点：在药品生产中确定和使用可持续溶剂：大多数药品从原料药到最终活性药物成分（API）需要多个操作（步骤）。在每一步中，通常需要不同的溶剂。这些溶剂可能有毒且处理成本高，在每一步分离产品时也会使用溶剂，从而增加成本。SolvIT将使用计算机建模和实验相结合的方法来评估在新药合成中最常用的化学反应中更可持续的替代溶剂，以便新的和现有的工艺可以使用这些新溶剂，减少浪费和成本。2. 集成溶剂和工艺设计：基于第一个目标的输出，我们将再次将计算建模方法与工艺设计结合起来，由一系列关键指标驱动，允许药物生产中的多个步骤组合或“伸缩”，最大限度地减少产生的浪费，并减少生产时间，从而从这两种改进中节省总体成本。3. 利益相关者参与：我们将与制药公司合作伙伴和行业监管机构合作，更好地从他们那里了解溶剂回收目前的障碍，并与他们沟通这项工作中出现的可能有助于克服这些障碍的新发展。这些研究链的整合，以及来自两个合作机构的跨学科合成化学、计算化学和化学工程的合作专业知识，将提供对整个制药行业特别是化学品制造领域有益的发现。

It may be surprising to learn, but the pharmaceutical industry is around 1000 times worse than oil refining in terms of waste generated per kg of product; the industry produces around 100kg of hazardous waste per kg of product, most of which is solvent. The proposed "SolvIT" bid will build on existing collaborations between Strathclyde and Imperial College in the area of modelling and solvent design, whilst strengthening the team with new collaborative partners, to tackle this colossal amount of waste. Our vision is to improve efficiency and reduce waste in the manufacture of new and existing medicines, lowering their cost, and making their production more sustainable and environmentally friendly. We plan to do this through three main programmes of work: 1. The identification and deployment of sustainable solvents in medicines manufacture: most medicines require multiple operations (steps) to go from bulk raw material to final active pharmaceutical ingredient (API). At each step, a different solvent is often required. These solvents may be toxic and costly to dispose of, isolation of products at each step, also incurring solvent use, adds to the cost. SolvIT will use a combination of computer modelling and experiment to evaluate alternative solvents, which are more sustainable, in the most popular chemical reactions used in the synthesis of new medicines, so that new and existing process can use these new solvents, reducing waste and cost. 2. Integrated solvent and process design: building on the outputs from the first objective, we will again combine computational modelling approaches with process design, driven by a range of key metrics, to allow multiple steps in the medicine production to be combined, or "telescoped", minimising the waste that is generated, and reducing time to production, resulting in overall cost savings from both of these improvements. 3. Stakeholder engagement: we will engage with pharmaceutical company partners, and industry regulators, to better understand from them the current barriers to solvent recycling and communicate to them new developments emerging from this work which may help to overcome these barriers. The integration of these strands of research, along with the collaborative expertise from the two partner institutions, across disciplines of synthetic chemistry, computational chemistry, and chemical engineering, will deliver findings that will be of benefit across pharmaceutical industry in particular, and the chemicals manufacturing space in general.