Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats

Abstract

We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

“…Also felbinac (transdermal therapeutic system) and diclofenac (spray gel), two topical drugs for treatment of muscle inflammation, have been examined using MD. Based on the high drug concentrations found in the skin and subcutaneous tissues, respectively, both administration modalities were shown to be possible alternatives to orally administered nonsteroidal anti-inflammatory drugs for superficial muscle inflammation [91,117] . Ketoprofen penetration kinetics following application as a transdermal therapeutic system (with the target being intra-articular inflammation) has been measured in the skin as well as in the knee joint by MD.…”

Design and Evaluation of a Novel Felbinac Transdermal Patch: Combining Ion-Pair and Chemical Enhancer Strategy

“…As a potent NSAID, felbinac (FEL) has been widely used for treatment of osteoarthritis, rheumatoid arthritis, muscle inflammation, and acute soft tissue injuries in topical preparations [4][5][6][7]. Currently, FEL patches have been available in Japan and Korea, but the product has a large application area of 70 cm 2 , which is far beyond the desired size (that is, a surface area of ≤40 cm 2 ) and decreased patients' compliance [8].…”

Crosstalk the Microdialysis in Scientific Research: from Principle to its Applications

“…In the recent years, there were many articles reported for the tumor necrosis factor(TNF-α), IL-1,IL-6,IL-8, prostaglandin (PG), iso-prostaglandin F(2)-IsoPs, histamine and other inflammatory cytokines [90][91][92][93][94] to carry out the MD sampling, so as could evaluate the local anti-inflammatory drug pharmacodynamics. Shinkai et al [95] using the croton oil to establish the rat skin inflammation model, after the MD probe was implanted in the subcutaneous, then given the felbinac patch, the MD sample drug concentration was measured, wherein the PGE-2 levels were measured, the results showed that croton oil significantly increased the subcutaneous PGE-2 levels, while providing 0.5% or 3.5% felbinac patch after 2~5 h, the PGE-2 levels were significantly decreased. In Shinkai et al [96] another study had proven that the transdermal ketoprofen significantly reduced the PGE-2 skin content and the joint fluid.…”