Producing Pharmaceutical Particles via Electrospraying with an Emphasis on Nano and Nano Structured Particles - A Review

Abstract

Recent advances in nanotechnology offer nano sized or nanostructured pharmaceutical particles, being as small as the size of cells such as receptors or nucleic acids, which can be engineered to provide enhanced efficacy, solubility, or biocompatibility, and to administer at much lower dosages. However, industrial production of these particles is still challenging. Among different techniques, aerosol based ones might be favorable since they are considered as contamination free processes and do not interfere with complex molecules of drugs. We, in this review, consider liquid atomization, where droplet formation is followed by conversion into solid particles. The best candidate is a method, which not only produces mono sized droplets with a diameter smaller than the inside nozzle diameter but also generates small enough start up sizes. Such a method is found in: Electro-Hydrodynamic Atomization (EHDA) or Electrospraying. Electrospraying is now a well practiced technique for producing very fine monodisperse droplets from a liquid under the influence of electrical forces. By controlling the liquid flow rate and the electrostatic potential between the liquid and the counter electrode, droplets within a narrow size range can be generated, while the mean diameter ranges from nanometers up to several micrometers. Besides generating monodisperse droplets, electrosprays are also distinguished by their self dispersing nature due to Coulomb repulsion, the possibility of trajectory control of the produced charged droplets, and the reduced risk of nozzle clogging due to the large size of the orifice compared to the size of the droplets. We will discuss different spraying modes depending on the strength of the electric stresses relative to the surface tension stress on the liquid surface and on the inertia of the liquid leaving the nozzle. However, for the production of monodisperse nanoparticles the so called cone-jet mode will be explained in depth. Scaling laws can be used to estimate the operational conditions for producing nanodroplets of a certain size. Hartman and coworkers refined the scaling laws for EHDA in the Cone-Jet mode using theoretically derived models for the cone, jet, and droplet size. By means of several examples, a generic way to produce nanoparticles, via scaling laws, from a multitude of different precursors will be discussed. Several examples of medicine particles with different properties made by EHDA will be given. Processes based on bipolar coagulation, where oppositely charged carrier particles and nano sized active agents are brought together to form composite drugs, will be discussed. Finally some attention will be given to challenges on out-scaling of EHDA methods for industrial production.