Medicine Nanoparticle Production by EHDA

Abstract

Chemical products, in general, can be produced in the liquid or gas phase. However for most medicines, with their complex molecules, the liquid route will be the appropriate one. To make these medicines into nanoparticles can also be done via the wet route (colloids) or a dry route. To separate the nanoparticles from the liquid phase will be almost impossible without some contamination, so to avoid contamination a dry method might be favourable. So to be considered is the disintegration of bigger structures into (nano) fractions. Depending on the phase of the structures, liquid or solid, different disintegration techniques exist, such as grinding, liquid atomization, lithography and etching, and evaporation/condensation. Only attention will be given here to liquid atomization with the consequent droplet to particle conversion. From the several atomization methods we are only interested in methods which break up into rather uniform droplets, so we limit ourselves to jet breakup in the laminar flow region (Lefebvre 1989). Another limitation is the size of the initially generated droplets. To produce nanoparticles the initial droplet size should be already fairly small, because otherwise the begin concentration has to be unacceptably low. One should realize that the diameter of the final particle after drying equals the diameter of the initial droplet times the cube root of the volumetric concentration of the non-volatile material (van Erven et al. 2005). So in case of very low concentrations of the product material, the role of impurities might become very important. For methods, where atomization is brought about by forcing liquid through a thin nozzle or orifice, such as for the Vibrating Orifice Aerosol Generator (TSI Model 3450) the generated droplet size will be about two times the orifice diameter, while the orifice size is restricted by clogging risk. So the best option is a method, which produces mono sized droplets with a diameter smaller than the inside nozzle diameter. Such a method is found in: ElectroHydrodynamic Atomization (EHDA) or Electrospraying. EHDA is a method to produce very fine droplets from a liquid (atomization) by using an electric field. By applying the right conditions, monodisperse droplets from nanometers to several micrometers can be produced. By means of an example, i.e., the production of nano platinum particles, a generic way to produce nanoparticles from a multitude of different precursors is given. After that, several examples of medicine particles made by EHDA will be given, in the nano- and micro-range, with different properties, such as controlled release, high porosity and elongated shape. Also a method, bipolar coagulation, where two sprays of opposite electrical potential are used will be discussed. In this method, each combination of a positive and a negative charged droplet can be seen as a nano- or micro-reactor, so being able to produce new chemical compounds in a liquid, aerosolized condition. Bipolar coagulation can also be used to apply nanoparticles on a carrier. Finally some attention will be given on EHDA instrumentation and out-scaling methods.