Novel Methods of Microparticulate Production: Application to Drug Delivery

Abstract

The purpose of this paper is to present two novel techniques, electrostatic spraying and oscillating capillary nebulization, for the production of microspheres of uniform reproducible particle size distribution. Cholesterol was chosen as a model compound to show the utility of both procedures. The processes for each method are described, illustrating their simplicity and absence of an external detrimental phase. Scanning electron microscopy was used to assess morphology while laser diffraction analysis was used to determine particle size. Electrostatic spraying of cholesterol yielded particles of round shape, smooth surface, and uniform distribution of particle size ranging between 10-30 microns and 100-300 microns. Oscillating capillary nebulization of cholesterol molten at 170 degrees C produced microspheres with an average diameter ranging from 22 microns to 30 microns when gas back pressures controlling the vibration of the capillary ranged from 60 to 90 psi. Electrostatic spraying and oscillating capillary nebulization are one-step procedures that result in high production yields. Both techniques are easy to set up and afford both production speed and reproducibility. The absence of a detrimental external phase makes them particularly appealing for the microencapsulation of proteins and polynucleotides in polymers with low melting temperatures. The feasibility of production of cholesterol microspheres can be extrapolated to the production of excipient-free microspheres of steroids.