Microparticle Formation Kinetics in Spray Drying

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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.