Particle engineering principles and technologies for pharmaceutical biologics.

The global market of pharmaceutical biologics has expanded significantly during the last few decades. Currently, pharmaceutical biologic products constitute an indispensable part of the modern medicines. Most pharmaceutical biologic products are injections either in the forms of solutions or lyophilized powders because of their low oral bioavailability. There are certain pharmaceutical biologic entities formulated into particulate delivery systems for the administration via non-invasive routes or to achieve prolonged pharmaceutical actions to reduce the frequency of injections. It has been well documented that the design of nano- and microparticles via various particle engineering technologies could render pharmaceutical biologics with certain benefits including improved stability, enhanced intracellular uptake, prolonged pharmacological effect, enhanced bioavailability, reduced side effects, and improved patient compliance. Herein, we review the principles of the particle engineering technologies based on bottom-up approach and present the important formulation and process parameters that influence the critical quality attributes with some mathematical models. Subsequently, various nano- and microparticle engineering technologies used to formulate or process pharmaceutical biologic entities are reviewed. Lastly, an array of commercialized products of pharmaceutical biologics accomplished based on various particle engineering technologies are presented and the challenges in the development of particulate delivery systems for pharmaceutical biologics are discussed.