Microparticle Formation Kinetics in Spray Drying

喷雾干燥中的微粒形成动力学

• 批准号: RGPIN-2016-04111
• 负责人: Vehring, Reinhard
• 金额: $ 2.77万
• 依托单位: University of Alberta
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=708920
• 关键词: Microparticle; Formation; Kinetics; Spray; Drying

Particle Engineering provides the analytical and theoretical basis for the design of advanced microparticles. These small particles have applications in many fields, e.g. in the chemical and food industries. One application in particular has grown steadily over the last decade, the design of inhalable microparticles for drug delivery to the nose or lung. Several therapeutics based on these particles have entered the market or are in late stage pharmaceutical development. Particle engineering methodology has been implemented in the industrial development process. Advanced microparticles typically have diameters in the range of 0.5 50 µm and are structured, i.e. they have functional substructures often in the nanometer scale, which impact important product attributes such as physical and chemical stability, encapsulation, or powder flowability and dispersibility, i.e., the property of a powder that describes how easy it is to disperse it into individual particles. The most developed manufacturing technique for structured microparticles is spray drying. Much progress has been achieved in understanding relevant sub-processes and the effect of process parameters on product attributes. Theoretical models for process control and diffusion controlled solid particle formation have been developed and implemented. Yet the kinetics of precipitation events during the solidification of drying microdroplets remain poorly understood. This lack of basic understanding has resulted in a partially empirical approach in the industrial development process. This approach is time and resource consuming and has the tendency to increase early development risk, timelines, and budget. This provides the motivation to study particle formation kinetics in depth, develop models for key processes such as nucleation and crystallization, apply the results to the design of novel process equipment, and ultimately to enable the design of a new class of particle based products. Particle formation events will be studied in the well controlled model environment of a chain of identically sized droplets generated by an inkjet-type droplet generator. The droplets will be injected into a controlled laminar gas flow. While drying their diameter can be measured optically and the final particles can be sampled for ultramicroscopic analysis. Molecular spectroscopy, specifically in situ low frequency shift Raman spectroscopy, will be used to identify and quantify solid phases and the amount of order in the drying particles. A numerical code that can describe drying processes with variable evaporation rate, surface activity, and precipitation processes will be developed and used to interpret the experimental results and for the development of predictive models. Larger powder quantities of microparticles will be produced under controlled drying kinetics using a novel spray dryer.

粒子工程为高级微粒设计提供了分析和理论基础。这些小颗粒在许多领域都有应用，例如在化学和食品行业中。在过去的十年中，尤其是一种应用程序，是一种可吸入的微粒的设计，用于递送到鼻子或肺部。基于这些颗粒的几种疗法已经进入市场或正在晚期药物开发。粒子工程方法论它们通常的直径在0.5 50 µm的范围内并且结构化，即它们经常在纳米尺度上具有功能性子结构，这会影响重要的产品属性，例如物理和化学稳定性，封装，粉末流动性和分散性和分散性，即描述粉末易于易于分散的粉末。 结构化微粒最发达的制造技术是喷雾干燥。在理解相关子过程以及过程参数对产品属性的影响方面取得了很多进展。已经开发和实施了用于过程控制和扩散控制的固体颗粒形成的理论模型。然而，在干燥微螺旋体的凝固过程中降水事件的动力学仍然知之甚少。缺乏基本的理解导致了工业发展过程中的部分经验方法。这种方法是时间和资源消耗，并且倾向于增加早期发展风险，时间表和预算。这提供了深入研究粒子形成动力学的动机，诸如成核和结晶等关键过程的开发模型，将结果应用于新型工艺设备的设计，并最终使新的基于粒子的产品的设计。 粒子形成事件将在由喷墨型液滴发生器产生的相同大小的液滴链的良好控制模型环境中进行研究。液滴将被注入受控的层流气流。虽然可以通过光学测量干燥直径，并且可以对最终颗粒进行采样以进行超显微镜分析。分子光谱法，特别是原位低频拉曼光谱法，将用于识别和量化固体相位和干燥颗粒中的顺序量。将开发并使用具有可变经济速度，表面活动和精度过程的干燥过程的数值代码，并用于解释实验结果和开发预测模型。使用一种新型喷雾干燥器，将在受控干燥动力学下生产较大的粉末量。