MICRONISATION OF TOBRAMYCIN USING DENSE GAS ANTI-SOLVENT TECHNIQUES

摘要

The feasibility of micronising tobramycin by the gas anti-solvent technique was investigated, The micronisation of tobramycin was carried out by precipitating from a solution using dense gas anti-solvent techniques. Two different techniques, the Gas Anti-Solvent (GAS) method and the Aerosol Solvent Extraction System (ASES) were utilised. Tobramycin was dissolved in an organic solvent such as methanol, ethanol and dimethyl sulfoxide. In the GAS process the solution was expanded with CO_2 at 25℃ and 35℃ with pressures ranging from 50 to 70 bar. In the ASES process the solution was sprayed into a vessel pressurised with carbon dioxide at 25℃ and 45℃ with the density of 0.017 and 0.018 gmol/cm~3. Sub-micron particles of tobramycin were produced using both techniques. The GAS technique produced uniform micro-spheres that had a low degree of agglomeration. The ASES technique produced smaller particles that were highly agglomerated and in some cases, of irregular morphology. The results of in vitro analysis indicated the fine particle mass ( < 5 micron) was at least 40%. It is therefore possible to use the drug for dry powder inhalation delivery.