The size and unique surface properties of pharmaceutical nanoparticles offer substantial therapeutic benefits in dissolution and controlled release. These properties may be designed with novel precipitation processes including controlled precipitation with an antisolvent, spray freezing into liquid nitrogen and thin film freezing. For poorly water soluble drug nanoparticles, high surface areas and stable amorphous polymorphs enhance thermodynamic and kinetic properties of dissolution. Smart surfactants are being designed to: (1) control particle nucleation, growth and stabilization, and (2) facilitate in vitro and in vivo wetting and dissolution behavior in the GI tract or lungs. Stable protein nanoparticles on the order of 100 to 500 nm offer new opportunities for controlled release in parenteral and pulmonary delivery. Protein aggregation is largely avoided by minimizing the time of exposure to air-water and glass-water interfaces. The particle size is controlled by manipulating the nucleation and growth rates, as a function of the droplet/film geometry and cooling rate.

A novel concept is presented for the formation of stable suspensions composed of very low density flocs of rod-shaped drugs in hydrofluoroalkane propellants for pressurized meter dose inhalers (pMDI), and for templating the flocs to achieve high fine particle fractions in pulmonary delivery. Bovine serum albumin (BSA) nanorods are shown by theory and experiment to form space filling flocs with protein particle volume fractions of only 0.0020, which are one order of magnitude lower than for flocs composed of spheres. The rods are flocculated reversibly. Upon atomization, 25 micron HFA droplets break apart and template the highly open flocs, which are held together by extremely weak van der Waals forces. Upon evaporation of the HFA, capillary forces shrink the ~25 micron templated flocs resulting in porous particles with optimal = 3-4 microns for deep lung delivery. This novel concept for forming extremely stable suspensions of open flocs of rod shaped particles, and templating and shrinking the flocs to produce particles for efficient pMDI deep lung delivery is applicable to a wide variety of drugs without the need for surfactants or cosolvents to stabilize the primary particles.