The in vitro delivery of NSAIDs across skin was in proportion to the delivery of essential fatty acids in the vehicle—evidence that solutes permeate skin associated with their solvation cages?

• Published in: International journal of pharmaceutics 2003-08, Vol.261 (1), p.165-169
• Main Authors: Heard, Charles M, Gallagher, Simon J, Harwood, John, Maguire, Paula B
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Arthritis; Chromatography, High Pressure Liquid; Docosahexaenoic Acids - pharmacokinetics; Eicosapentaenoic Acid - pharmacokinetics; Fish oil; Fish Oils; Ibuprofen; Ibuprofen - pharmacokinetics; In Vitro Techniques; Ketoprofen; Ketoprofen - pharmacokinetics; n−3 fatty acids; Permeability; Pharmaceutical Vehicles; Skin Absorption; Swine; Transcutaneous delivery; Vehicle
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(03)00297-7

As part of our investigations into novel dual action topical anti-arthritis systems, the permeation of ibuprofen or ketoprofen plus eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were determined from a fish oil vehicle across pig ear skin in vitro. The steady state fluxes of ibuprofen and ketoprofen were 9.17±1.98 μg cm −2 h −1 and 6.12±2.39 μg cm −2 h −1, respectively. At 24 h, 5.7 μg cm −2 EPA and 3.1 μg cm −2 DHA permeated when the solute was ibuprofen; 1.4 μg cm −2 EPA and 1.0 μg cm −2 DHA when ketoprofen was the solute. At 12 h, the ketoprofen/ibuprofen ratio of the moles permeated was 0.27, the ratio of EPA permeated simultaneously with ketoprofen and ibuprofen was 0.22 and the ratio of DHA permeated simultaneously with ketoprofen and ibuprofen was 0.24. We believe this is the first time that simultaneous permeation across skin of a solute and its vehicle has been determined purposefully. The data successfully demonstrated that simultaneous permeation of NSAIDs and essential fatty acids, EPA and DHA from a formulation containing fish oil is feasible. In addition, for both NSAIDs, the relative rates of permeation of EPA and DHA, were in proportion to their levels in the fish oil and the permeation rate of either fatty acid was higher when the permeation rate of the solute was greater. This suggested that the greater the rate of permeation of the NSAID, the greater the rate of permeation of the vehicle, and that a solute permeates skin complete with its vehicular solvation cage. This apparent relationship between solute and vehicle fluxes may be of more widespread significance to skin permeation experimentation.