Investigation of Mass Transfer Phenomena in Supercritical Antisolvent Precipitation Processes

Abstract

This dissertation involves a detailed discussion of the production of organic and polymeric microparticles of controllable size and size distribution for several applications including certain pharmaceutical formulations. Particle size and particle size distribution are two key factors for the performance of active pharmaceutical ingredients. The supercritical antisolvent (SAS) precipitation process is one of the methods used to produce microparticles. SAS is performed by spraying a solution of an organic solvent and a solute through nozzle into a supercritical antisolvent. The solute is insoluble in the antisolvent and the organic solvent is soluble the antisolvent. The organic solvent and the antisolvent mix as the solution is sprayed which leads to supersaturation of the solute. This causes the solute to precipitate out as small particles. The underlying phenomena of these processes are not fully understood which results in poor control of the particle formation. This research is focused on improving our understanding the mechanisms of particle formation in supercritical antisolvent precipitation processes. A high magnification visualization system was used to study the effects of process conditions on the spray characteristics and microparticles in the SAS precipitation process, quantifying drop size in SAS spray in an effort to examine solvent/antisolvent mass transfer. We carried out a number of SAS experiments to determine the relationship between the SAS spray characteristics and the particle characteristics. To study the effects of pressure, temperature and density of the antisolvent on the produced particles, 1 wt% polymethyl methacrylate (PMMA) in acetone, 1 wt% budesonide in ethanol and varying compositions of 1wt% PMMA+budesonide in acetone were processed via the SAS precipitation process. From these studies we found that spray characteristics were altered significantly by varying operating conditions, however, the resulting particle characteristics were relatively consistent for a range of operating conditions and spray characteristics. Thus, the ability to control the nature of the process spray is insufficient to control the particle characteristics, and as such, other phenomena are heavily influencing the particle characteristics in the SAS precipitation process. To better control this precipitation process, a clearer understanding of the mass transfer and concentration fields in this process is required.