Stability, anti-inflammatory effect and percutaneous absorption of indomethacin in absorption ointment formulations

Abstract

Both the topical and percutaneous anti-inflammatory activities of absorption ointment formulations containing indomethacin were investigated in rabbits. Indomethacin absorption ointment significantly inhibited the formation of granuloma and decreased edema on the dorsal skin induced by a subcutaneous injection of carrageenin. The determination of indomethacin and its hydrolysis products such as p-chlorobenzoic acid and 5-methoxy-2-methyl-3-indole acetic acid from an ointment was proposed by using reversed-phase HPLC and UV detection. The apparent first-order rate constant can be obtained accurately and easily by using the Weibull probability paper, and was used to predict the stability of indomethacin in an ointment. The stability increased in proportion to the concentration of polysorbate 20 or polysorbate 80. However, a marked decrease in the percutaneous absorption of indomethacin occurred with the absorption ointment base containing a concentration of 4.62% polysorbate 20. But the additional concentration of polysorbate 80 below 4.62% did not produce any significant change in percutaneous absorption of indomethacin.