Skin permeation of indomethacin from gel formed by fatty-acid ester and phospholipid

We selected 20 fatty-acid esters from cosmetic ingredients and investigated their suitability as a vehicle for absorption-type ointments using indomethacin (IM) as a model drug. Five fatty-acid ester groups, octanoate, isononanoate, myristate, palmitate and stearate, were selected. The total number of carbon atoms in the fatty-acid esters ranged from 17 to 34, and all of these esters are liquid at room temperature except stearyl caprylate. The solubility of IM was higher in fatty-acid esters containing fewer carbon atoms. The permeation rate of IM from a fatty-acid ester suspension through excised hairless rat skin was proportional to its solubility in the suspension, i.e. about 1-3 mu g/cm(2)/h. Gels were then formed from esters by the addition of a hydrogenated phospholipid. The permeation rate of IM from gels were 4-20 mu g/cm(2)/h which were higher than those from suspensions because IM was present in amorphous state with phospholipid. High permeation rates from gels of fatty-acid esters in which side chains were present on both fatty-acid and alcohol moieties were observed.