Controlling drug nanoparticle formation by rapid precipitation.

Nanoparticles are a drug delivery platform that can enhance the efficacy of active pharmaceutical ingredients, including poorly-water soluble compounds, ionic drugs, proteins, peptides, siRNA and DNA therapeutics. To realize the potential of these nano-sized carriers, manufacturing processes must be capable of providing reproducible, scalable and stable formulations. Antisolvent precipitation to form drug nanoparticles has been demonstrated as one such robust and scalable process. This review discusses the nucleation and growth of organic nanoparticles at high supersaturation. We present process considerations for controlling supersaturations as well as physical and chemical routes for modifying API solubility to optimize supersaturation and control particle size. We conclude with a discussion of post-precipitation factors which influence nanoparticle stability and efficacy in vivo and techniques for stabilization.