Particle Fabrication Techniques for Pharmaceutical Applications

Abstract

In the present work, Electrohydrodynamic Atomization was employed to produce biodegradable polymeric microparticles in a new generation of shuttle glass chamber. The effects of different operational parameters on the particle collection efficiency and residual amount of organic solvent in collected particles were investigated systematically. The Taguchi method was used to design the experiments. It was found that the important factors affecting particle collection efficiency were given in the following orders: solution flow rate, nitrogen flow rate, ring, and nozzle voltage. It was found that solution flow rate and nozzle voltage can considerably affect the size of fabricated particles. A computational model (using FLUENT and COMSOL as computational fluid dynamic software) was developed in this study to simulate the fluid and particle dynamics in an EHDA chamber. It was found that nitrogen flow rate, solution flow rate and voltage difference between the nozzle and ring can significantly affect the particle collection efficiency of the EHDA process. Electric field and electric potential profiles in the chamber were significantly affected by the combined voltages of the nozzle and ring. The computational model developed in this study provided a means of understanding the various processes involved in particle fabrication using the EHDA methodology. In a new set of experiments, an additional aluminum plate was located a few centimeters above the collecting plate in EHDA chamber which was connected to positive high voltage generator. This work aimed to investigate the effect of the auxiliary electric field on particle collection efficiency, morphology and size distribution. The final results show that application of the auxiliary electric field can clearly enhance particle collection efficiency in comparison to the EHDA process without auxiliary electric field. Additionally, it was established that the particle size distribution was not considerably influenced by the auxiliary electric field. On the contrary, the smoothness of the particles can be affected by the auxiliary electric field especially when a high voltage is applied to the flat plate. Scaling analysis was used to assess the relative importance of the terms in the particle force balance. The collection efficiency of the EHDA process was determined from a force balance on the particles that in turn depends on the fluid dynamics and electric field. It led to a unique dimensionless group that permits collapsing all the experimental data for the effect on the particle collection efficiency of the carrier gas flow rate, liquid solution flow rate and electric field strength onto a generalized plot. Electrospray deposition on a substrate through a mask, to generate biodegradable polymeric particle patterns, was also considered in this study to investigate the effect of different operational parameters. Moreover, a mathematical model was developed to track the particle trajectories and focusing effect in electrospray deposition process on the substrate. The final results confirm that the clearest particle pattern and the best focusing effect on the substrate can be achieved with long distance between the nozzle and the substrate, high voltage difference between the nozzle and the mask, short process time and low solution flow rate. Furthermore, micro-fibers can be observed on the mask when the voltage difference between the nozzle and substrate is not high.

In the last part of this study, Electrical Capacitance Tomography (ECT) was used for insitu monitoring of very dilute pharmaceutical droplet and particle trajectories in different regions of EHDA encapsulation chamber. A new type of ECT sensor with internal and external electrodes was used to improve the sensitivity of ECT measurement for detection of the objects in the central area of the EHDA encapsulation chamber.