title: Occlusion effect on transcutaneous NSAID delivery from conventional and carrier-based formulations.
abstract: 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 (0.086cmh(-1)) marginally exceeds the value for the drug from carriers in a gel (0.058cmh(-1)), which resembles conventional gel on open excised skin (0.057cmh(-1)); smallness of occlusion-induced permeation enhancement ( approximately 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 approximately 15xlower (0.004cmh(-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 approximately 35-fold. The AUC for occluded ultradeformable, hydrophilic carriers measured in living pigs is conversely approximately 10x lower, being 1.4-2.2x below that of the tape that is inferior to non-occluded carriers formulation (normalised cmax: approximately 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 is thus evidently well differentiated and innovative.
authors.affiliation: IDEA AG, Frankfurter Ring 193a, D-80807 Munich, Germany, EU. info@idea-ag.de
authors.forename: Gregor
authors.initials: G
authors.lastname: Cevc
authors.forename: Stefan
authors.initials: S
authors.lastname: Mazgareanu
authors.forename: Matthias
authors.initials: M
authors.lastname: Rother
authors.forename: Ulrich
authors.initials: U
authors.lastname: Vierl
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005782:Gels; D057927:Hydrophobic and Hydrophilic Interactions; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D012869:Skin Absorption; D013552:Swine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005782:Gels; D007660:Ketoprofen