Production of Drug Nanoparticles of Controllable Size Using Supercritical Fluid Antisolvent Technique with Enhanced Mass Transfer

The use of supercritical fluids in the area of material processing and for particle formation has been known for several years now. The advantages of supercritical fluid processing include mild operating temperatures, production of solvent free particles and easy micro encapsulation of particles. One of the attractive methods of particle processing using supercritical fluid is the Supercritical Antisolvent (SAS) technique. Although this technique has numerous advantages, it still cannot produce fine particles in the sub-micron range (<300 nm) for soft materials. A significant improvement in the SAS process has been proposed in this work, to obtain particles of controllable size that are up to ten-fold smaller and have narrower size distributions. Like the conventional SAS technique, the new technique Supercritical Antisolvent Precipitation with Enhanced Mass Transfer (SAS-EM) also utilizes supercritical carbon dioxide as the antisolvent, but in this case the solution jet is deflected by a surface vibrating at an ultrasonic frequency, that atomizes the jet into much smaller droplets. Furthermore, the ultrasound field generated by the vibrating surface enhances mass transfer and prevents agglomeration through increased mixing. The particle size is easily controlled by varying the vibration intensity of the deflecting surface, which can be adjusted by changing the power supplied to the attached ultrasound transducer. This new technique is demonstrated by the formation of nanoparticles of different pharmaceuticals such as lysozyme, tetracycline and griseofulvin. INTRODUCTION Nanoparticles are important in developing delivery systems for controlled release of drugs. These systems can improve the therapeutic efficacy of drugs, in-vitro and in-vivo stability, bioavailability, targetability, and bio-distribution to reduce toxicity [1]. The delivery systems involving nanoparticles studied so far include, polymer nanoparticles with the drug dispersed within the polymer matrix, drug nanoparticles coated with a biodegradable polymer, polymer nanoparticles with the drug adsorbed on the surface, and nanoparticle suspensions for poorly soluble drugs [2]. There have been several methods in the past for the manufacture of drug nanoparticles. Some of the conventional techniques include spray drying and ultra fine milling [3, 4]. The major disadvantage of these techniques is that they produce particle having a broad size distribution (0.5 25 μm) and only a small fraction of the particles produced are in