PARTITIONING AND DIFFERENTIAL SCANNING CALORIMETRY STUDIES OF N-ALKYLLACTAME ESTER DERMAL PRODRUGS OF INDOMETHACIN

The mechanism of indomethacin percutaneous absorption enhancement by N -alkyllactam eater prodrugs (esters I-III) was investigated by assessi ng stratum corneum partitioning and solubility together with diffusion parameters of both indomethacin and its prodrugs. Skin diffusional ch aracteristics of indomethacin and its esters were evaluated on the bas is of their apparent diffusion coefficients and their interaction, ass essed by differential scanning calorimetry, with multilamellar liposom es of dipalmitoylphosphatidylcholine. From the results obtained, the e nhancement ability of esters I and II could be attributed to their gre ater stratum corneum solubility associated with better diffusion chara cteristics compared to the parent drug, while the enhancement effect o f ester III could be due only to its higher diffusion coefficient.