权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Pressure-Induced Nucleation for the Continuous Manufacture of supramolecular assemblies

用于连续制造超分子组装体的压力诱导成核

基本信息

批准号：
EP/N015401/1
负责人：
Iain Oswald
金额：
$ 123.11万
依托单位：
University of Strathclyde
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FN015401%2F1
关键词：
Pressure Induced Nucleation Continuous Manufacture

项目摘要

The organic solid state is at the centre of a number of key billion dollar industries from pharmaceuticals ($60 billion, 2009); pigments and dyes ($1.2 billion revenue, 2010), agrochemicals ($134 billion market, 2010), energetics (explosives and propellants; $0.5 billion revenue, 2012). Each of these industries suffers from attrition whereby the number of possible products that reach the marketplace is a fraction of those conceived and made in research labs. A stage at which materials are discarded is that of the physicochemical properties. A well-known example is in the pharmaceutical industry where it is estimated that it costs $1.6 billion to produce one drug compound which is due, in part, to the catastrophic attrition rates of drug products from bench to production line. Therefore if there was a method by which one could alter the physicochemical properties without changing the functionality of the molecules the cost for manufacture would decrease considerably. Crystal Engineering or co-crystallisation is one method by which one can alter the properties of materials by forming supramolecular assemblies. These assemblies contain more than one chemical entity but can enhance stability, solubility, colour and flow properties through the addition of the second inert component. The inclusion of a second component impacts on the three-dimensional arrangement of molecules which in turn changes the physical properties of materials. The beauty of this method is that the functionality of the molecule in question is not changed i.e. a pharmaceutical product still possesses the correct molecular geometry to bind to receptors to affect a response; the solubility of a pigment may be enhanced without the loss of its colour. Another method by which one can alter the three-dimensional structure of a material hence its physical properties is via the application of high-pressure (pressures of >1atm). High pressure has proven to be an extremely effective method for changing the 3-D structure and industrial high pressure methods are already in use for pasteurising foodstuffs e.g. chicken, shellfish, orange juice etc. One of the key disadvantages is that new high pressure forms of single-component materials, e.g. paracetamol, are not stable under normal working conditions. By coupling the two areas of science together, crystal engineering and high pressure, we will be able to create materials that are stable under normal working conditions. This proposal seeks to develop a novel manufacturing methodology by which we are able to form new materials at high pressure and feed these into an industrial scale process. This process of 'seeding' is used in industrial settings presently to ensure that a consistent product is formed from the crystallisation process, we will use this process to promote the growth of high-pressure materials under ambient conditions in both batch and continuous flow systems. The latter system would align our project to the outputs of the EPSRC Centre for Continuous Manufacture and Crystallisation. Furthermore, detailed analysis of the process and the resulting materials will be carried out so that improvements can be made in the process, such as the pressures and concentrations used, as well as the design of the assemblies themselves. The physical properties of the new materials will be investigated and will provide the feedback to improve upon the process.

有机固态是许多关键的十亿美元产业的核心，包括制药（600亿美元，2009年）;颜料和染料（12亿美元收入，2010年），农用化学品（1340亿美元市场，2010年），能源（炸药和推进剂; 5亿美元收入，2012年）。这些行业中的每一个都遭受着损耗，即到达市场的可能产品的数量是研究实验室中构思和制造的产品的一小部分。材料被丢弃的阶段是物理化学性质的阶段。一个众所周知的例子是在制药行业，据估计，生产一种药物化合物的成本为16亿美元，部分原因是药品从实验室到生产线的灾难性损耗率。因此，如果有一种方法可以改变物理化学性质而不改变分子的功能，那么制造成本将大大降低。晶体工程或共结晶是一种通过形成超分子组装体来改变材料性质的方法。这些组件包含多于一种的化学实体，但可以通过添加第二惰性组分来增强稳定性、溶解度、颜色和流动性质。包含第二组分影响分子的三维排列，这反过来改变了材料的物理性质。该方法的优点在于所讨论的分子的功能性没有改变，即药物产品仍然具有正确的分子几何结构以结合受体以影响响应;可以增强颜料的溶解度而不损失其颜色。另一种可以改变材料的三维结构从而改变其物理性质的方法是通过施加高压（压力> 1个大气压）。高压已被证明是改变3-D结构的极其有效的方法，并且工业高压方法已经用于对食品（例如鸡肉、贝类、橙子汁等）进行巴氏灭菌。其中一个关键缺点是，新的高压形式的单组分材料（例如扑热息痛）在正常工作条件下不稳定。通过将晶体工程和高压这两个科学领域结合在一起，我们将能够创造出在正常工作条件下稳定的材料。该提案旨在开发一种新的制造方法，通过这种方法，我们能够在高压下形成新材料，并将其投入工业规模的过程。目前，这种“引晶”工艺用于工业环境中，以确保从结晶过程中形成一致的产品，我们将使用这种工艺在批量和连续流系统中的环境条件下促进高压材料的生长。后一个系统将使我们的项目与EPSRC连续制造和结晶中心的产出保持一致。此外，将对工艺和所得材料进行详细分析，以便改进工艺，例如所用的压力和浓度，以及组件本身的设计。新材料的物理性能将被调查，并将提供反馈，以改进工艺。