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 approximately 3.5 x 10(-3) cm h(-1) at 24h) below that of conventional gels ( approximately 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 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 < or =1.6% for conventional topical NSAID gels and merely approximately 0.05% for Diractin. In contrast, in vivo ketoprofen transport by ultradeformable carriers through non-occluded 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.
IDEA AG, Frankfurter Ring 193a, D-80807 Munich, Germany. info@idea-ag.de
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D000287:Administration, Topical; D000465:Algorithms; D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001693:Biological Transport, Active; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005782:Gels; D006801:Humans; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D010316:Particle Size; D012869:Skin Absorption; D013056:Spectrophotometry, Ultraviolet; D013535:Suspensions; D013552:Swine
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005782:Gels; D013535:Suspensions; D007660:Ketoprofen