title: Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels.
abstract: We compared in vivo transport and biodistribution of ketoprofen applied on the skin in ultradeformable carriers (Diractin) or a conventional topical gel (Gabrilen) with oral drug (Oruvail); for reference we used in vitro study data. The drug from Gabrilen diffuses into body with low bioavailability (<10%) and limited regio-selectivity (AUC(deep muscle/plasma) approximately 45/0.8 (t=0-8h), reaching maximum concentration in subcutaneous tissues and plasma at similar time (t(max) approximately 3-4h). The apparent drug elimination half-life is then similar to oral ketoprofen (t1/2,a) approximately 2 h). In contrast, Diractin containing ultradeformable carriers (Transfersome vesicles) delivers the drug more efficiently (>50%) and more directly into peripheral muscles (AUC(deep muscle/plasma) approximately 447/0.7 (652/1.4) for t=0-8 (0-24)h; tmax approximately 1 h), arguably in non-diffusive fashion. Ketoprofen from Diractin moreover disappears from body periphery slower (t1/2,a) approximately 4-6 h), owing to sustained drug release from the carriers in target tissue. Final clearance always proceeds via plasma (tmax approximately 4 h). Epicutaneous application of ketoprofen in conventional gels or the carrier-based formulation thus leads to different local accumulations and clearances. Ketoprofen from Diractin achieves more desirable biodistribution and clearance, arguably due to spontaneous carrier-mediated drug transport across the skin, which ensures local and relatively long-lasting drug deposition into peripheral target tissues.
authors.affiliation: IDEA AG, Frankfurter Ring 193a, D-80807 Munich, Germany. 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
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005079:Excipients; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D013056:Spectrophotometry, Ultraviolet; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D007660:Ketoprofen