title: Continuous contact- and contamination-free ultrasonic emulsification-a useful tool for pharmaceutical development and production.
abstract: 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 microm 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 microm 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.
authors.affiliation: Institute of Pharmaceutical Sciences, ETH Zürich-Hönggerberg, 8093 Zürich, Switzerland.
authors.forename: Sergio
authors.initials: S
authors.lastname: Freitas
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hielscher
authors.forename: Hans P
authors.initials: HP
authors.lastname: Merkle
authors.forename: Bruno
authors.initials: B
authors.lastname: Gander
mesh_terms: D005591:Chemical Fractionation / Q000295:instrumentation* / Q000379:methods; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D004340:Drug Contamination / Q000517:prevention & control; D004655:Emulsions / Q000138:chemical synthesis* / Q000528:radiation effects; D004867:Equipment Design; D019544:Equipment Failure Analysis; D017022:Flow Injection Analysis / Q000295:instrumentation* / Q000379:methods; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000528:radiation effects; D013010:Sonication / Q000295:instrumentation*
chemical_list: D004655:Emulsions; D004364:Pharmaceutical Preparations