Production of nanosuspensions as a tool to improve drug bioavailability: focus on topical delivery

Over the past two decades nanosizing technology has become one of the most successful formulation approaches for improving the bioavailability of poorly soluble drugs, which show a low oral absorption due to low dissolution velocity. Nanocrystals are nanoparticles of pure drug, without any matrix material, with an average diameter below 1 μm (typically in the range of 200-500 nm), which can be prepared in both water and non-water media as colloidal nanosuspensions stabilized using surfactants or polymers. The reduction of the drug particle diameter below 1 μm increases the dissolution velocity by increasing the particle surface and decreasing the diffusion layer thickness. Nanosuspension production processes involve two different approaches such as bottom-up (drug nanocrystal precipitation) and top-down (drug particle disintegration) technologies or a combination of two. Within these main approaches, a variety of possible techniques to achieve particle size reduction have been proposed by different research groups from both industry and academia. Even though nanosuspensions formulations have been especially studied for oral and parenteral administration, nanocrystals have showed a great potential also for topical delivery through alternative routes such as dermal, pulmonary and ocular route. The purpose of this review is to describe the main technologies used to produce nanosuspensions as well as to explore the most significant results and progresses obtained by application of drug nanocrystal formulations through topical routes.