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

悬浮液中纳米颗粒产品的制造对制药、特种化学品和功能材料行业正变得越来越重要。例如，由于纳米级药物的溶解度和生物利用度显著提高，纳米加工现在被用作固体形式疏水药物的一种有效的给药方法。工业条件下纳米加工的最大挑战被强调为难以实现以粒度分布为特征的产品质量的一致性。这项拟议研究的目标是研究可在工业操作条件下应用的在线表征和过程建模技术。在线传感的研究将集中在用于实时颗粒测量的光子相关光谱和声波光谱。这项工作将解决多重散射和粒子-粒子相互作用带来的关键挑战，这是已知的导致高固体浓度下测量不正确的原因。高固体浓度不仅是商业生产纳米颗粒在经济上可行的范围(需要更大的反应器来处理相同数量的低浓度颗粒)，而且在技术上也是为许多工艺生产超细颗粒所必需的。在线实时测量将为使用人口平衡方程开发过程模型提供宝贵的数据。重点将是定量推导用于人口平衡方程的颗粒破碎和聚集模型，以及对数据的智能解释，以改进对这一过程的定性理解。选择的研究过程是湿法纳米研磨，这是制药、农用化学品和材料行业中处理纳米粒子的非常重要的操作。

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.