Nanoparticles are of importance in numerous technological applications. Given the markedly different physical, chemical and material properties of these solids compared to the bulk materials, new methodologies must be developed in order to generate, process and utilize particles of this nature. Conventional methods of producing small particles, such as spray drying, milling or lyophilization, have serious shortcomings. New particle technologies based on supercritical fluids, particularly the use of rapid expansion of supercritical solutions (RESS) and supercritical antisolvent (SAS), provide particles with a narrow size distribution in the 0.1-10 mm range. The particles are obtained free of organic solvents, and micro-encapsulation of different materials is straight forward. Unfortunately, none of these techniques can produce smaller particles in the 1-100 nm range. Interesting properties of nanoparticles are observed at these smaller sizes, and it is therefore important to explore possible improvements in the methods for producing them. In this proposal, a significant improvement to the SAS process is proposed. In this process, particles are produced by introducing a solution into a supercritical antisolvent. The mass transfer rate of the antisolvent into the solution is a key factor in obtaining a high supersaturation rate and smaller particle size, and it is the limiting factor in the present SAS technology. The proposed process, supercritical antisolvent with ultrasound (SASU), uses an ultrasound field (y-axis) orthogonal to the solution jet (x-axis). The ultrasound field provides a velocity component in the direction which greatly enhances the turbulence, resulting in a high mass transfer. It is expected that the fast rate of mixing of the antisolvent and solution in the SASU process will provide particles 100 fold smaller than those obtained from the SAS process alone. This technique will be demonstrated by the formation of nanoparticles of several polymers both with and without the encapsulation of other materials. If successful, the proposed process will provide a quantum advance in the manufacturing of nanoparticles.
| Chattopadhyay, P; Gupta, R B (2001) Production of griseofulvin nanoparticles using supercritical CO(2) antisolvent with enhanced mass transfer. Int J Pharm 228:19-31 |
