Industrial & Engineering Chemistry Research, Vol.41, No.8, 1993-2004, 2002
Micronization of copper indomethacin using gas antisolvent processes
The nonsteroidal antiinflammatory drug Cu-2(indomethacin)(4)L-2 [Cu-Indo; L = dimethylformamide (DMF)] was successfully micronized by the gas antisolvent technique (GAS) and aerosol solvent extraction systems (ASES) using DMF as the solvent and CO2 as the antisolvent. The effect of changing process variables on the size and morphology of the particles produced was investigated at temperatures between 25 and 40 degreesC, pressures between 6.6 and 14.5 MPa, and solute concentrations between 5 and 200 mg(.)g(-1). The most dominant variable was found to be solute concentration. As the Cu-Indo concentration was increased from 5 to 200 mg(.)g(-1), the morphology of the particles produced from the GAS process was changed from rhombic to bipyramidal. The particles obtained from the ASES process were changed from bipyramidal to spherical as the concentration was increased from 5 to 100 mg(.)g(-1). A further increase in the solute concentration to 200 mg(.)g(-1) resulted in large porous spheres when processing Cu-Indo by ASES. The nature of the solvent has a significant impact on the morphology of Cu-Indo in both GAS and ASES processes. The particle size of Cu-Indo produced by ASES was one-fifth of those produced by GAS. Spherical particles of Cu-Indo with diameters of less than 8 mum were formed at 24 degreesC and 6.39 MPa by processing solutions concentrated more than 20 mg(.)g(-1) using ASES. The immediate benefit of micronizing Cu-Indo was demonstrated with an eightfold increase in the dissolution rate in water compared with the unprocessed drug.