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.

纯化是化学制造中的一个重要过程，可确保仅获得所需的产品，并有效去除许多日常材料，它是制药、精细化学品、油漆、颜料中的主要纯化技术。英国化学工业营业额为 550 亿英镑，占英国制造业产值的 11%。 2012 年，英国制药业的贸易顺差为 55 亿英镑，出口额为 209 亿英镑。制造商按产品销售 (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，分子聚集在一起形成具有规则 3D 堆积排列（称为晶格）的晶体，通过溶液中的分子识别进行纯化。 - 晶格界面。在晶体表面的某些位置，杂质分子和晶格之间的失配非常大，以致于在其他位置，晶格失配足够小，杂质分子背离晶面的部分可能与相邻分子相差很大，从而破坏并减慢了后续的分子。增加结晶驱动力会导致杂质过度生长并掺入产品中，工业结晶的典型进料流含有百分之几的杂质，因此这些相互作用非常严重。有时，产品非常不纯，晶体生长的杂质中毒会增加处理时间，从而大大减慢达到平衡的速度，以致某些产品必须留在溶液中并损失在废物流中。通过提高产量和加速结晶过程来提高晶体纯度和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 工业结晶挑战和科学问题 9 月 12 日）。 2011）。在结晶过程中进行干预以去除生长晶体表面的杂质将克服这个问题，从而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，因为声音通过与每个分子的相互作用在介质中传播。 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生长晶体附近的分子运动，从而改善往返晶体面的传输。由空化事件引起的高度局部扰动会导致瞬时局部温度波动，当这些扰动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，尽管之前已经有过超声结晶的工作，但这是一个新领域。该应用将发展新的理解并带来新的工艺能力，该方法有利于批量工艺，但在连续工艺中尤其有价值，在连续工艺中，加速结晶将减少通常是最长工艺步骤的停留时间。对于批处理占主导地位的制药行业来说具有战略意义，但由于财务、质量和可持续性原因，有强烈的动力转向连续运营。在斯特拉斯克莱德大学开展该项目使其与包括 EPSRC 创新制造中心和在内的主要国家制造研究活动保持一致。连续制造和结晶博士培训中心 (CMAC) 以及造价 8900 万英镑的斯特拉斯克莱德大学技术与创新中心 (TIC) 内的专用设施，旨在促进连续加工，特别是结晶。

项目成果

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: http://dx.10.1007/978-94-024-1117-1_18
• 发表时间: 2022
• 期刊: Discover education
• 作者: Leung E

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

了解过滤和洗涤对干燥产品的影响：扑热息痛案例研究

• DOI: http://dx.10.1016/j.powtec.2020.02.064
• 发表时间: 2020
• 期刊: Powder Technology
• 影响因子: 5.2
• 作者: Ottoboni S

Developing a Batch Isolation Procedure and Running It in an Automated Semicontinuous Unit: AWL CFD25 Case Study.

开发批量隔离程序并在自动化半连续单元中运行：AWL CFD25 案例研究。

• DOI: http://dx.10.1021/acs.oprd.9b00512
• 发表时间: 2020
• 期刊: Organic process research & development
• 影响因子: 3.4
• 作者: Ottoboni S

Digital Design of Filtration and Washing of Active Pharmaceutical Ingredients via Mechanistic Modeling

通过机械建模进行活性药物成分过滤和洗涤的数字化设计

• DOI: 10.1021/acs.oprd.2c00165
• 发表时间: 2022-12-16
• 期刊: Organic Process Research & Development
• 影响因子: 3.4
• 作者: Ottoboni, Sara;Brown, Cameron J.;Mehta, Bhavik;Jimeno, Guillermo;Mitchell, Niall A.;Sefcik, Jan;Price, Chris J.
• 通讯作者: Price, Chris J.

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

了解 API 热气流静态干燥：干燥装置原型的设计和测试以及干燥建模开发。

• DOI: http://dx.10.1021/acs.oprd.0c00035
• 发表时间: 2020
• 期刊: Organic process research & development
• 影响因子: 3.4
• 作者: Ottoboni S