Terbutaline microparticles suitable for aerosol delivery produced by supercritical assisted atomization.

A new micronization technique called supercritical assisted atomization has been used to produce terbutaline microparticles with controlled particle size distribution in the range of drug particles deliverable by aerosol. The process is based on the solubilization of a fixed amount of supercritical carbon dioxide in a liquid solution; then, the ternary mixture is sprayed through a nozzle and atomized in order to produce microparticles. Water has been used as the liquid solvent; heated nitrogen has also been delivered into the precipitator to evaporate the liquid droplets. The process has been first optimized with respect to pressure and temperature (mixing temperature and pressure, precipitation temperature) and very mild operation conditions have been selected; then, the influence of the solute concentration in the liquid solution on particle size has been studied. The terbutaline produced powders were characterized with respect to morphologies and particle size. Spherical particles with very narrow volumetric particle size distributions were produced. Particularly, operating at 30 and 50mg of terbutaline per ml of water, more than 90% of the two distributions ranged between 1 and 3 microm; at 80 mg/ml more than 99% of the distribution ranged between 1 and 4 microm. HPLC analysis confirmed that no chemical degradation occurred in the drug as a consequence of the supercritical processing.