Preparation and characterization of microspheres containing the anti-inflammatory agents, indomethacin, ibuprofen, and ketoprofen

Abstract

The anti-inflammatory agents, indomethacin, ibuprofen, and ketoprofen, were encapsulated by the solvent evaporation method using polymers such as ethylcellulose, poly(ϵ-caprolactone), poly(methyl methacrylate), polystyrene, and Eudragit RS and RL. In vitro dissolution studies, scanning electron microscopy, and differential scanning calorimetry were used to characterize the microspheres. In contrast to the release of ibuprofen and ketoprofen, the release of indomethacin from ethylcellulose microspheres was too slow for oral use even at high drug loadings. The indomethacin release could be increased by using more permeable polymers or polymer blends. The rates of polymer and drug precipitation during microsphere formation were dependent upon the organic solvent selected. When chloroform was selected as the organic solvent, the drug precipitated before the polymer and indomethacin crystals were visible on the microsphere surface. With methylene chloride, the polymer precipitated before the drug, and drug crystals were not observed. The analysis of the microspheres by differential scanning calorimetry was inconclusive since the drugs dissolved in the molten polymer during the heating step. Indomethacin-poly(ϵ-caprolactone) microspheres were prepared by a melt-dispersion technique without the use of organic solvents.