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Effect of polysorbates on percutaneous absorption of indomethacin from ointment in rabbits.

Four kinds of polysorbates were incorporated into an absorption ointment base containing indomethacin. Percutaneous absorption was determined from plasma indomethacin levels in rabbits at regular interval for 14 hours following application of the ointment. Percutaneous absorption of indomethacin was decreased significantly when polysorbate 20 and 40 were added to the ointment. Four different concentrations of polysorbate 80 were studied: 2.3%, 4.62%; 6.93% and 15% (w/w). The lowest polysorbate 80 concentration (2.3%) did not produce any significant change in the percutaneous absorption of indomethacin. However, a decrease in drug absorption was observed after the addition of higher concentrations of polysorbate 80 at 6.93% or 15%. The absorption ointment base has poor drug-releasing effect, poor percutaneous absorption and promotes scarce reservation in the skin for indomethacin. This is due to the formation of many inclusion compounds of indomethacin with numerous micelles produced by the high concentration of polysorbate in the aqueous phase of the ointment.