Pharmacodynamic and pharmacokinetic evaluation of lipid microspheres of indomethacin.

Lipid microspheres (LM) of indomethacin were prepared using phosphatidyl choline and soya bean oil. LM of required size (< 1 micron) were obtained by intermittent microscopic observation while homogenization. Anti-inflammatory activity of lipo-indomethacin was compared with free indomethacin by carrageenan induced rat paw edema model. It was found that at 30% edema inhibitory dose, lipo-indomethacin was about 1.5 times more potent than free indomethacin, indicating possible localization of LM at the inflammatory site. Biodistribution studies were performed in rats at the dose of 12 mg/kg. After 2 h of the treatment, concentration of the drug was 0.31 microgram/g of inflammatory tissue with lipo-indomethacin, whereas, only 0.05 microgram/g of the tissue was found with free indomethacin. Maximum difference in drug concentrations between the above two formulations was observed in lungs. LM were found not to cross the BBB as drug concentration in the brain after lipo-indomethacin treatment was below the detectable level. Thus, the pharmacokinetic data gave a quantitative evidence for high anti-inflammatory potential of lipo-indomethacin.