Occlusion effect on transcutaneous NSAID delivery from conventional and carrier-based formulations

We studied skin occlusion effects in vitro and in vivo on local and systemic delivery of ketoprofen across the organ, using the drug in a conventional non-occlusive topical gel (Togal (R) Mobil-Gel), an occlusive tape (Mohrus (R)), and the new targeted analgesic (Diractin (R)), comprising ultradeformable, hydrophilic carriers in the form of a Transfersome (R) vesicle. In vitro occluded skin permeability to ketoprofen from the tape (0.086 cm h(-1)) marginally exceeds the value for the drug from carriers in a gel (0.058 cm h(-1)), which resembles conventional gel on open excised skin (0.057 cm h(-1));smallness of occlusion-induced permeation enhancement (similar to 1.5x) may be due to the high tested applied dose. In contrast, open skin permeability to the drug from the carriers in vitro is similar to 15x lower (0.004 cm h(-1)). The benefit of ketoprofen association with the carriers for targeted transcutaneous delivery only shows-up in vivo after an non-occlusive epicutaneous application: the area under the curve (AUC) in peripheral deep muscle for the carrier-based gel then exceeds AUC for conventional gel similar to 35-fold. The AUC for occluded ultradeformable, hydrophilic carriers measured in living pigs is conversely similar to 10x lower, being 1.4-2.2x below that of the tape that is inferior to non-occluded carriers formulation (normalised c(max): similar to 200x). Occlusion thus disables ultradeformable, hydrophilic carriers by eliminating transcutaneous hydration gradient that normally drives the carriers across the skin. Compared with other non-steroidal anti-inflammatory agents (NSAIDs) for local usage, Diractin (R) is thus evidently well differentiated and innovative. (C) 2008 Published by Elsevier B.V.