Mechanical particle-size reduction techniques

Abstract

With the increasing number of new drug candidates, the number of entities with poor aqueous solubility is on the rise. To overcome this limitation, a common formulation approach has been to decrease the particle-size of the drug. This strategy results in increased surface area, increased saturation solubility, and decreased the diffusional distance, all of which lead to an increase in the extent and the rate of dissolution. Mechanical techniques to decrease the particle-size of solids are generally classified in three categories: dry-milling, wet-milling, and high-pressure homogenization. In order to produce particles in the submicron (nano) range and further increase solubility, techniques such as wet-media milling, piston-gap homogenization, and microfluidization have been developed. More recently, combination technologies of both top-down and bottom-up approaches have gained much interest. All these different strategies will be reviewed and discussed in this chapter.