Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels

We compared in vivo transport and biodistribution of ketoprofen applied on the skin in ultradeformable carriers (Diractino) or a conventional topical get (Gabrilen') with oral drug (Oruvail'); for reference we used in vitro study data. The drug from Gabrilene diffuses into body with low bioavailability (<10%) and limited regio-selectivity (AUC(deep muscle/plasma) -45/0.8 (t=0-8h), reaching maximum concentration in subcutaneous tissues and plasma at similar time (tma -3-4h). The apparent drug elimination half-life is then similar to oral ketoprofen (tl/2, -2 h). In contrast, Diractino containing ultradefortnable carriers (Transfersomeo vesicles) delivers the drug more efficiently (>50%) and more directly into peripheral muscles (AUC(deep muscle/plasma) -447/0.7 (652/1.4) for t=0-8 (0-24)h; tma, -1h), arguably in non-diffusive fashion. Ketoprofen from Diractino moreover disappears from body periphery slower (tl/2.a -4-6 h), owing to sustained drug release from the carriers in target tissue. Final clearance always proceeds via plasma (t,,, -4h). Epicutaneous application of ketoprofen in conventional gels or the carrier-based formulation thus leads to different local accumulations and clearances. Ketoprofen from Diractine 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. (c) 2008 Published by Elsevier B.V.