Functional characterisation of novel analgesic product based on self-regulating drug carriers

We compared a new formulation of ketoprofen (Diractin (R)) based on ultradeformable vesicle (Transfersome0) carriers with conventional topical gels with the drug (Gabrileno; Togall Mobil Gel; Fastuml). Depending on water concentration, between a few percent and >95% of ketoprofen in Diractin' is associated with the vesicles. The low free drug concentration on open skin (1-3%) minimises ketoprofen diffusion from Diractin' through the organ, keeping effective permeability coefficient for the product (even after increase to -3.5 x 10-1 cm, h-1 at 24 h) below that of conventional gels (-0.3-2.1 x 10-1 cm h-1). The carrier's stress-responsiveness enables constriction crossing without vesicle breakdown. The carrier stiffening upon dilution, e.g. in tissues below the skin's diffusive barrier, helps avoiclingthe drug uptake in cutaneous blood capillaries. Diractin' therefore can deposit ketoprofen in deep subcutaneous tissues, which the drug from conventional gels reaches mainly via systemic circulation. In vitro efficacy of daily drug delivery through skin is < 1.6% for conventional topical NSAID gels and merely -0.05% for Diractin. in contrast, in vivo ketoprofen transport by ultradeformable carriers through nonoccluded skin into living pigs' subcutaneous muscles is 5-14x better than for conventional gels. Locally targeted drug transport by the self-regulating, ultradeformable vesicles is thus clearly non-diffusive and quite efficient. (c) 2008 Published by Elsevier B.V.