Micronization of antibiotics by supercritical assisted atomization

Supercritical assisted atomization (SAA) was used to produce tetracycline (TTC) and rifampicin (RF) microparticles with controlled particle size and particle size distributions in the range of aerosolizable drug delivery. The process is based on the solubilization of a fixed amount of supercritical carbon dioxide in the liquid solution; then the ternary mixture is sprayed thought a nozzle, and, as a consequence of atomization, solid microparticles are formed. Water was used as liquid solvent for TTC and methanol was used for RF; heated nitrogen was also delivered into the precipitator in order to evaporate the liquid droplets and generate the microparticles. SAA of these compounds was optimized with respect to the process parameters; then, the influence of the solute concentration in the liquid solution on particle size and particle size distribution was studied. The produced powders were characterized with respect to their morphologies and particle size: spherical particles with controlled particle size ranging between 0.5 and 3 pm were obtained for both drugs at optimized operating conditions. HPLC and GC-Head Space analyses confirmed that no chemical degradation occurred in the drugs after the SAA processing and, in the case of methanol, a solvent residue of 5 ppb remained in the product. The X-ray traces revealed that all the SAA micronized powders were amorphous whereas the untreated material shows crystalline patterns. (C) 2002 Elsevier Science B.V. All rights reserved.