Electrohydrodynamic atomization and spray-drying for the production of pure drug nanocrystals and co-crystals

In recent years, nanotechnology has offered attractive opportunities to overcome the (bio)pharmaceutical drawbacks of most drugs such as low aqueous solubility and bioavailability. Among the numerous methodologies that have been applied to improve drug performance, a special emphasis has been made on those that increase the dissolution rate and the saturation solubility by the reduction of the particle size of pure drugs to the nanoscale and the associated increase of the specific surface area. Different top-down and bottom-up methods have been implemented, each one with its own pros and cons. Over the last years, the latter that rely on the dissolution of the drug in a proper solvent and its crystallization or co-crystallization by precipitation in an anti-solvent or, conversely, by solvent evaporation have gained remarkable impulse owing to the ability to adjust features such as size, size distribution, morphology and to control the amorphous/crystalline nature of the product. In this framework, electrohydrodynamic atomization (also called electrospraying) and spray-drying excel due to their simplicity and potential scalability. Moreover, they do not necessarily require suspension stabilizers and dry products are often produced during the formation of the nanoparticles what ensures physicochemical stability for longer times than liquid products. This review overviews the potential of these two technologies for the production of pure drug nanocrystals and co-crystals and discusses the recent technological advances and challenges for their implementation in pharmaceutical research and development.