Transforming Industrial Crystallization by Sono-mechanical Manipulation of Crystal Surfaces

通过晶体表面的声机械操作来改变工业结晶

• 批准号: EP/L014971/1
• 负责人: Christopher Price
• 金额: $ 136.53万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FL014971%2F1
• 关键词: Transforming; Industrial; Crystallization; Sono; mechanical

Purification is a vital process in chemical manufacture that ensures only the desired product is obtained and unwanted or hazardous impurities are effectively removed. Many every day materials are purified by crystallization. It is the principal purification technique in the pharmaceutical, fine chemical, paint, pigment and agrochemical sectors. The UK chemical industry turnover is £55 billion or 11% of the value of UK manufacturing. The UK pharmaceutical sector generated a trade surplus of £5.5 billion in 2012 with exports of £20.9 billion. (UK Manufacturers' Sales by Product (PRODCOM) 2011 (ONS December 2012) & HMRC UK Trade Information June 2013).During crystallization molecules assemble together to form crystals with a regular 3D packing arrangement known as a lattice. Purification occurs by molecular recognition at the solution - lattice interface. At some sites on the crystal surface the mismatch between the impurity molecule and the lattice is so large that the impurity is rejected. At other sites the lattice mismatch is small enough for the impurity to attach to the crystal face. The portion of the impurity molecule facing away from the crystal face may differ so much from the adjacent molecules that it disrupts and slows the subsequent growth on that crystal face. Increasing the crystallization driving force results in the impurity being overgrown and incorporated into the product. Typical feed streams to industrial crystallizations contain several % of impurities so these interactions are very frequent and have serious consequences. Sometimes the product is so impure it has to be re-crystallized. Impurity poisoning of crystal growth increases processing time slowing the approach to equilibrium so much that some product has to be left in solution and lost in the waste stream. Improving crystal purity and increasing efficiency through improved yield and accelerating crystallization processes are amongst the major challenges identified by the European Federation of Chemical Engineering Working Party on Crystallization, (Biscans Industrial Crystallization Challenges and Scientific Issues Sept 2011).Intervening to remove impurities from the growing crystal surface during crystallization will overcome this problem increasing product purity and productivity, reducing waste and delivering crystals with improved performance. Ultrasound is uniquely suited to this task as sound propagates through media by interaction with every molecule present. Frequencies in the KHz to MHz range are high enough to intervene as each molecular layer is added to the growing crystal. The proposed mechanisms involve increased molecular motion adjacent to the growing crystal improving transport to and from the crystal faces. Highly localised perturbations caused by cavitation events lead to momentary local temperature fluctuations. When these occur close to strained regions of the lattice where impurities are attached they favour release of the impurity molecules. Although there has been previous work sonocrystallization this is a new area of application that will develop new understanding and lead to a new process capability. The approach benefits batch processes but will be especially valuable in continuous processes where accelerating crystallization will reduce residence time in what is usually the longest process step. This is strategic for the pharmaceutical sector where batch processing dominates but there is a strong drive to switch to continuous operation for financial, quality and sustainability reasons. Undertaking this project at Strathclyde University aligns it with major national manufacturing research activities including the EPSRC Centre for Innovative Manufacturing and Doctoral Training Centre in Continuous Manufacturing and Crystallisation (CMAC) and dedicated facility within the £89M University of Strathclyde Technology and Innovation Centre (TIC) designed to promote continuous processing, particularly crystallization.

纯化是化学品生产中的一个重要过程，可确保仅获得所需的产品，并有效去除不需要的或有害的杂质。许多日常材料都通过结晶进行纯化。它是制药、精细化工、油漆、颜料和农用化学品行业的主要净化技术。英国化学工业的营业额为550亿英镑，占英国制造业价值的11%。2012年，英国制药业产生了55亿英镑的贸易顺差，出口额为209亿英镑。(UK制造商销售产品（PRODCOM）2011年（ONS 2012年12月）和HMRC英国贸易信息2013年6月）。在结晶过程中，分子组装在一起形成晶体，具有规则的3D堆积排列，称为晶格。纯化通过溶液-晶格界面处的分子识别发生。在晶体表面的某些位置，杂质分子和晶格之间的失配是如此之大，以至于杂质被排斥。在其他位置，晶格失配足够小，杂质可以附着在晶面上。背向晶面的杂质分子部分可能与相邻分子有很大不同，以致于它会破坏并减缓随后在该晶面上的生长。增加结晶驱动力导致杂质过度生长并掺入产物中。工业结晶的典型进料流含有几%的杂质，因此这些相互作用非常频繁并具有严重的后果。有时候产品太不纯了，不得不重结晶。晶体生长的杂质中毒增加了处理时间，使达到平衡的速度减慢，以至于一些产物不得不留在溶液中并在废物流中损失。通过提高产量和加速结晶过程来提高晶体纯度和提高效率是欧洲化学工程联合会结晶工作组确定的主要挑战之一，（Biscans Industrial Crystallization Challenges and Scientific Issues Sept 2011）在结晶过程中从生长的晶体表面去除杂质的干预将克服这个问题，提高产品纯度和生产率，减少浪费并提供具有改进性能的晶体。超声波是唯一适合这项任务的声音传播通过媒体的相互作用与每一个分子存在。KHz到MHz范围内的频率足够高，可以在每个分子层添加到生长晶体时进行干预。所提出的机制涉及增加邻近生长晶体的分子运动，改善往返晶面的运输。由空化事件引起的高度局部化扰动导致瞬时局部温度波动。当这些发生在靠近杂质附着的晶格应变区域时，它们有利于杂质分子的释放。虽然已经有以前的工作sonoconversion这是一个新的应用领域，将开发新的理解，并导致一个新的过程能力。该方法有利于间歇工艺，但在连续工艺中尤其有价值，其中加速结晶将减少通常最长工艺步骤中的停留时间。这对于制药行业具有战略意义，因为批量处理占主导地位，但出于财务、质量和可持续性原因，转向连续操作的动力很强。在斯特拉斯克莱德大学进行这个项目使其与主要的国家制造业研究活动保持一致，包括EPSRC创新制造中心和连续制造和结晶博士培训中心（CMAC）以及斯特拉斯克莱德技术和创新中心（TIC）的8900万英镑大学内的专用设施，旨在促进连续加工，特别是结晶。

项目成果

The Effect of Ultrasound on the Crystallisation of Paracetamol in the Presence of Structurally Similar Impurities

存在结构相似杂质时超声波对扑热息痛结晶的影响

• DOI: 10.3390/cryst7100294
• 发表时间: 2017
• 期刊: Crystals
• 影响因子: 2.7
• 作者: Nguyen T

Understanding effect of filtration and washing on dried product: Paracetamol case study

• DOI: 10.1016/j.powtec.2020.02.064
• 发表时间: 2020-04-15
• 期刊: POWDER TECHNOLOGY
• 影响因子: 5.2
• 作者: Ottoboni, S.;Simurda, M.;Price, C. J.
• 通讯作者: Price, C. J.

Understanding API Static Drying with Hot Gas Flow: Design and Test of a Drying Rig Prototype and Drying Modeling Development.

• DOI: 10.1021/acs.oprd.0c00035
• 发表时间: 2020-11-20
• 期刊: Organic process research & development
• 影响因子: 3.4
• 作者: Ottoboni S;Coleman SJ;Steven C;Siddique M;Fraissinet M;Joannes M;Laux A;Barton A;Firth P;Price CJ;Mulheran PA
• 通讯作者: Mulheran PA

Social support in schools and related outcomes for LGBTQ youth: a scoping review.

LGBTQ 青少年的学校社会支持和相关成果：范围界定审查。

• DOI: 10.1007/978-3-319-06935-7_16
• 发表时间: 2022
• 期刊: Discover education
• 作者: Leung E

Elucidating the mechanism of paracetamol sonocrystallization for product purity enhancement

阐明对乙酰氨基酚超声结晶提高产品纯度的机制

• DOI: 10.1121/2.0000739
• 发表时间: 2017
• 作者: Forbes C