(360e) A Hydrodynamic Method for the Production of Nanoparticles

Authors: 
Muzzio, F. J., Rutgers University


Recent advances in the ability to structure material on the nano-meter size scale offer the pharmaceutical industry a new tool set: (i) high potency drugs can be made into small controlled release spheres which can survive in the body for a long period and slowly release there payload keeping a steady safe concentration in the body (ii) low solubility (lipophilic) compounds can be made into nano-sized spheres which will have a very high surface area to volume ratio for improved solubility (iii) nano-sized drug carriers can be surface modified with specific proteins to target specific areas of uptake and greatly reduce the occurrence of side effects. While creating these functionalities is already a difficult task at the laboratory scale, scaling-up these techniques to the manufacturing scale poses a whole new set of challenges.

In this talk we focus on a method for creating nano sized particles at a rate suitable for full-scale manufacturing. The basic mechanism of the Hydrodynamic Formation pathway is the creation of a nano-emulsion of which the droplets can be hardened to form nano-particles. The droplets of the emulsion are either the therapeutic agent themselves or the therapeutic agent and an encapsulation material. Initially the emulsion is rough and the droplets are on the micron size scale. The emulsion is passed through a static mixer at a high rate. The shear inside the mixer causes the micron-sized drops to be reduced down into the 50-1000 nano-meter range. After the size reduction the droplets are hardened by a phase shift brought about by a rapid change in temperature or solubility conditions, or by extracting a solvent.

This work focuses on identifying the critical parameters for control the width and size of the particles produced by the high intensity process.