Continuous contact- and contamination-free ultrasonic emulsification - a useful tool for pharmaceutical development and production

A novel concept was developed here for the continuous, contact- and contamination-free treatment of fluid mixtures with ultrasound. It is based on exciting a steel jacket with an ultrasonic transducer, which transmitted the sound waves via pressurised water to a glass tube installed inside the jacket. Thus, no metallic particles can be emitted into the sonicated fluid, which is a common problem when a sonotrode and a fluid are in direct contact. Moreover, contamination of the fluid from the environment can be avoided, making the novel ultrasonic flow-through cell highly suitable for aseptic production of pharmaceutical preparations. As a model system, vegetable oil-in-water emulsions, fed into the cell as coarse pre-emulsions, were studied. The mean droplet diameter was decreased by two orders of magnitude yielding Sauter diameters of 0.5 mu m and below with good repeatability. Increasing the residence time in the ultrasonic field and the sonication power both decreased the emulsion mean diameter. Furthermore, the ultrasonic flow-through cell was found to be well suited for the production of nanoparticles of biodegradable polymers by the emulsion-solvent extraction/evaporation method. Here, perfectly spherical particles of a volume mean diameter of less than 0.5 mu m could be prepared. In conclusion, this novel technology offers a pharmaceutically interesting platform for nanodroplet and nanoparticle production and is well suited for aseptic continuous processing. (c) 2004 Elsevier B.V. All rights reserved.