Processing Nanoparticles in Suspension of High Solid Concentration: On-line Characterisation and Process Modelling

悬浮液中纳米颗粒形式产品的制造对于制药、特种化学品和功能材料工业变得越来越重要。例如，纳米加工现在被用作固体形式疏水性药物的有效药物递送方法，这是由于在纳米尺度下显著增加的药物溶解度和生物利用度。在工业条件下纳米加工的最大挑战是难以实现以粒度分布为特征的产品质量的一致性。这项研究的目的是调查在线表征和过程建模技术，可以应用于工业操作条件下。在线测量的研究将集中在光子相关光谱和声学光谱的实时颗粒尺寸。这项工作将解决多重散射和粒子-粒子相互作用所带来的关键挑战，这是导致高固体浓度下测量不正确的原因。高固体浓度不仅是纳米颗粒商业化生产的经济可行范围（需要大得多的反应器来处理相同量的低浓度颗粒），而且在技术上对于许多工艺生产超细颗粒至关重要。在线实时测量将提供宝贵的数据的过程模型的发展，使用人口平衡方程。重点将是定量推导用于人口平衡方程中的颗粒破碎和聚集模型，以及对数据的智能解释，以提高对该过程的定性理解。选择用于调查的过程是湿法纳米研磨，这是在制药、农业化学和材料工业中处理纳米颗粒的非常重要的操作。

Manufacture of nanometre particulate form products in suspensions is becoming increasingly important to the pharmaceutical, speciality chemical, and functional material industries. For instance, nano-processing is now used as an effective drug-delivery method for solid form hydrophobic pharmaceuticals due to the dramatically increased drug solubility and bioavailability at nano-scale. The biggest challenge to nano-processing under industrial conditions has been highlighted as the difficulty in achieving consistency in product quality as characterised by particle size distribution. The objective of this proposed research is to investigate on-line characterisation and process modelling techniques that can be applied under industrial operational conditions. The research on on-line sensing will focus on photon correlation spectroscopy and acoustic spectroscopy for real-time particle sizing. The work will tackle the key challenge posed by multiple scattering and particle-particle interactions, which are known to be the cause leading to incorrect measurement at high solid concentrations. High solid concentration is not only the economically viable range for commercial manufacture of nanoparticles (a much larger reactor would be required to process the same amount of particles in low concentration), but also technically essential for producing ultra-fine particles for many processes. The on-line real-time measurement will provide invaluable data to the development of process models using population balance equations. The focus will be on quantitatively deriving models for particle breakage and aggregation to be used in the population balance equations, as well as intelligent interpretation of the data to improve the qualitative understanding of the process. The process chosen for investigation is wet nano-milling, a very important operation for processing nanoparticles in the pharmaceutical, agrochemical and materials industries.