(585a) Nanoparticle Fabrication of Biodegradable Polymers Using Supercritical Antisolvent: Effects of Mixing and Thermodynamic Properties

One of the most important applications of supercritical fluid technology for the last 2 decades is particle formation [1]. Methods for particle formation using supercritical fluids include rapid expansion of supercritical solutions (RESS) [1-3] and the supercritical antisolvent (SAS) process [1, 2, 4-10]. CO2 is a great choice for processing pharmaceutical products due to its relatively accessible critical point (Tc = 31.1 oC and Pc = 73.8 bar) and its low toxicity [1-2]. Since most organic solvents are miscible with supercritical CO2, a low residual solvent content can be achieved in the final product. There have been many studies carried out using SAS with variations in the spraying process. More recent developments include the use of ultrasonic liquid atomization. This includes the work of Randolph et al. [4] and Subramanian et al. [5], who explored the use of ultrasonic nozzles to create mono-disperse solution droplets in supercritical CO2. Chattopadhyay and Gupta [6-10] used an ultrasonic vibrating surface to break up the solution jet into smaller droplets and also increase the mass transfer rates between supercritical CO2 and the solvent. This has been termed the Supercritical antisolvent with enhanced mass transfer process (SASEM). Considerable literature suggests that the controlling parameter for particle size in the SAS process is the rate of mass transfer [11].

In this study, poly L lactide (PLLA) and polycaprolactone (PCL) are used to fabricate nanoparticles using a process similar to the SASEM process. An ultrasonic vibrating probe (3/8? probe tip diameter) is fitted into the high pressure vessel to generate mixing and turbulence within the vessel. The organic phase is introduced into the high pressure vessel via a 440 micron ID stainless steel capillary. The spray is directed away from the ultrasonic vibrating probe tip. The high pressure vessel has borosilicate glass windows which allow observation of the SAS process.

The effects of ultrasonic vibration amplitude on the extent of mixing in the high pressure vessel and the resulting effects on particle sizes have been investigated. Studies with PLLA have shown that, without sonication, highly polydispersed particles are obtained. When sonication is applied during the SAS process, more monodispersed powders are obtained, and the sizes of the particles decrease with increasing ultrasonic vibration amplitude. The effects of varying temperature and pressure are also investigated.

These results provide a better understanding of the mass transfer effects during the SAS process so that optimal process conditions may be employed.

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