테녹시캄의 피부 흡수율을 증진시키기 위한 에탄올아민염의 제조

Abstract

The aim of this work was to prepare tenoxicam-ethanolamine salt with improved physicochemical properties, to compare the flux of tenoxicam and the tenoxicam-ethanolamine salts in various penetration enhancers and to investigate the drug flux from acrylic adhesive matrix with various functional groups for transdermal application. Tenoxicam-ethanolamine salt was prepared in methylene chloride and its physicochemical properties were investigated by DSC and FT-IR. The broad peak of tenoxicam around 3600-3200 cm-1 was shifted to lower wavenumber and more broadened. The melting peak of tenoxicam, tenoxicam-monoethanolamine salt and tenoxicam-diethanolamine salt appeared at 223, 159 and 146oC, respectively. In contrast to relatively small difference in the partition coefficients of tenoxicam and the tenoxicam-ethanolamine salt, large difference in aqueous solubility was observed. Crovol PK40 (PEG-12 palm kernel glycerides) provided the highest skin flux for both compounds. The order of the enhancing effect of the various vehicles tested was similar for tenoxicam and tenoxicam-ethanolamine salt, which indicated that their enhancing mechanism for tenoxicam and tenoxicam-ethanolamine salt is similar. Tenoxicam-ethanolamine salt had a higher skin flux than tenoxicam by 1.2- to 31.7-fold, depending on the vehicles used. It is suggested that the vehicles with medium HLB value, 1 double bond, and lower ethylene oxide chain length have a better ability to modify the permeability of the stratum corneum and to promote the effective penetration of tenoxicam and tenoxicam-ethanolamine salt. To compare the enhancing effect of various vehicles, the permeations of tenoxicam, tenoxicam-monoethanolamine salt and tenoxicam-diethanolamine salt from a supersaturated solution of various vehicles across hairless mouse skin were investigated. Labrafil 2609, Crovol A40 and Crovol? PK40 provided higher skin flux in all the compounds tested. The order of the enhancing effect of the various vehicles tested was similar for most of the compounds tested, except Crovol EP40. The drug flux was relatively higher in tenoxicam-monoethanolamine salt than tenoxicam-diethanolamine salt and tenoxicam. The effect of the chemical nature of acrylic adhesive matrices on the permeation of tenoxicam across hairless mouse skin was evaluated. The fluxes were significantly lower when compared to those obtained from solution formulations. The acrylic adhesive with a hydroxyl functional group and that with a non-functional group tend to provide a higher permeation rate. The acrylic adhesive with a carboxyl functional group provided the lowest permeation rate.