Partitioning and differential scanning calorimetry studies of N- alkyllactame ester dermal prodrugs of indomethacin

The mechanism of indomethacin percutaneous absorption enhancement by N-alkyllactam ester prodrugs (esters I-III) was investigated by assessing stratum corneum partitioning and solubility together with diffusion parameters of both indomethacin and its prodrugs. Skin diffusional characteristics of indomethacin and its esters were evaluated on the basis of their apparent diffusion coefficients and their interaction, assessed by differential scanning calorimetry, with multilamellar liposomes of dipalmitoylphosphatidylcholine. From the results obtained, the enhancement ability of esters I and II could be attributed to their greater stratum corneum solubility associated with better diffusion characteristics compared to the parent drug, while the enhancement effect of ester III could be due only to its higher diffusion coefficient.