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

We compared a new formulation of ketoprofen (Diractin®) based on ultradeformable vesicle (Transfersome®) carriers with conventional topical gels with the drug (Gabrilen®; Togal® Mobil Gel; Fastum®). 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 × 10−3 cm h−1 at 24 h) below that of conventional gels (∼0.3–2.1 × 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 avoiding the 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 non-occluded skin into living pigs’ subcutaneous muscles is 5–14× better than for conventional gels. Locally targeted drug transport by the self-regulating, ultradeformable vesicles is thus clearly non-diffusive and quite efficient.