Characteristics of transdermal topical delivery patch (MILTAX) containing the anti-inflammatory and analgestic drug, ketoprofen

Abstract

The characteristics of MILTAX®, a poultice-type patch containing ketoprofen, are here evaluated with reference to formulation, pharmacological and clinical aspects. Included is a comparison of skin permeation of ketoprofen with that of indometacin and piroxicam. The flux of ketoprofen was higher than that of other two drugs, while indometacin showed high skin permeability, but low saturated solubility, and therefore relatively poor skin permeation, L-menthol was found to be useful not only for enhancement of skin permeation, but also for giving a cool feeling to the skin. Atomic force microscopic (AFM) observations here revealed the existence of micro-domains sized a few nanometer in diameter on the surfaces of hydrophilic gels like MILTAX®. Moreover, ketoprofen might exist as micelles surrounded by polyoxyethylene sorbitan trioleate (PST) which could play an important role in both skin permeation and maintaining drug stability. The adhesion characteristics, probe tack, sticking strength and cohesion strength, were weaker with the poultice-type patch, MILTAX®, than with KP-T. In generally, the permeation of drugs is lower with human than with animal skin. Similarly, the flux of ketoprofen from MILTAX® for rat skin was 2∼3 times higher than with human skin. The release of ketoprofen from the patch was approximately 60∼70% at 24hour, with a relative bioavailability (BA) of 80∼90% in comparison with oral administration. The muscle concentration of ketoprofen after MILTAX® application was twice that after oral administration. No severe toxicity was seen in the primary and 7-day cumulative skin irritation tests in rabbits. Clinically, MILTAX® shows comparable anti-inflammatory and analgestic efficacy to oral administration of ketoprofen, but with much reduced side effects.