Microsphere formation in droplets using antisolvent vapour precipitation technique
thesisposted on 02.03.2017, 01:28 by Chew, Sean Jun Liang
In previous studies, the antisolvent vapour precipitation method has been proven to produce uniformly sized lactose microspheres (1.0 µm) from a single droplet (1.2 mm diameter) at atmospheric pressure. These types of particles have potential applications in the pharmaceutical industry, especially due to their high dissolution rate. This project looked into the possibility of using antisolvent vapour precipitation to produce microspheres from finely atomised droplets. Microspheres in the sub-micron scale (0.4 μm diameter) have been produced by this method, much smaller than those obtained from the single droplet method (1.0 μm diameter). The microsphere formation only occurred above a certain threshold of antisolvent concentration. Below this threshold, different structures were formed e.g.: porous, bicontinuous, ridges or coagulated structures. On the other hand, the formation of these particles were not affected by exposure time to ethanol vapour (up to 60 s) or drying temperature (up to 190oC). A two-phase system (caused by self-emulsification of the components in the droplets) was theorised as the mechanism responsible for the formation of the porous and bicontinuous structure., This theory was further reinforced as proven by the successful microsphere formation at higher antisolvent vapour concentrations, which was caused by a shrinkage phenomenon of the solute containing phase in the droplet. In the second part of this study, the effect of temperature variation during precipitation on particle formation was studied. Different temperature profiles were simulated using sets of Peltier modules to control direction of heat flow in or out of the chamber. No trend could be discerned from the different temperature profiles studied; microspheres appeared to form regardless of how fast the temperature increased or decreased over time. Nevertheless, an increase in the overall temperature reduced the concentration of antisolvent threshold required to precipitate microspheres from the atomised droplets. This discovery could be linked to the increased rate of evaporation in the droplet at higher temperatures; this led to an increased rate of antisolvent concentration rise in the droplets, which could indicate that this rate could be the determining factor in the type of particle structure formed. The results obtained from this study would be useful in determining the optimal parameters to produce microspheres using this approach in larger scale applications e.g. spray drying. Microspheres were successfully precipitated from smaller atomised droplets with a much smaller time scale, which would be advantageous for steady state processes.