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® Mobil-Gel), an occlusive tape (Mohrus®), and the new targeted analgesic (Diractin®), comprising ultradeformable, hydrophilic carriers in the form of a Transfersome® 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 (∼1.5×) may be due to the high tested applied dose. In contrast, open skin permeability to the drug from the carriers in vitro is ∼15× 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 ∼35-fold. The AUC for occluded ultradeformable, hydrophilic carriers measured in living pigs is conversely ∼10× lower, being 1.4–2.2× below that of the tape that is inferior to non-occluded carriers formulation (normalised cmax: ∼200×). 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® is thus evidently well differentiated and innovative.