"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 Fedtion 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."