| Summary: | 博士 === 高雄醫學大學 === 藥學研究所 === 96 === Meloxicam is a potent, newer nonsteroidal anti-inflammatory drug and used in treatment of reheumatoid arthritis, osteoarthritis and degenerative joint disease. Although meloxicam preferentially inhibits cyclooxgenease-2 over cyclooxgenease-1, it still has parts of incidence of gastrointestinal side effect. In order to reducing side effect of meloxicam, we developed the transdermal delivery system. In view of the characteristics of meloxicam including small
oral dose, low molecular weight, higher lipid solubility and excellent tissue tolerability, it seems that there is potential for investigating the meloxicam transdermal dosage as an additional route for meloxicam administration. In this study, the mixed-solvent and different types of penetration enhancers were used to enhance the penetration rate and decrease the lag time. In order to speedily obtain the optimal formulation, a computer optimization technique, based on a response surface methodology (RSM) utilizing polynomial equation was used to search for the optimal meloxicam formulation and efficiently quantify the influences of formulation variables on the drug permeation. The uniform design was applicable to prepare systematic model formulations which were composed of three formulation factors: the content of azone (x1), sodium lauryl sulfate (x2), and menthol (x3). The result showed that azone had the most potential influence on the percutaneous absorption of meloxicam. The response surface methodology was used to obtain an appropriate mixed-solvent system of pH-7.4 buffer and ethanol for preparing meloxicam hydrogel. The mixed-solvent system of pH-7.4 buffer and ethanol had a synergistic effect on the increase of drug solubility. The highest solubility was obtained in the ratio of 50/50 pH 7.4 buffer/ethanol. The enhancement effects of terpenes on drug precautious absorption were evaluated via in vitro and in vivo study. A series of terpenes were used as enhancer for improving the penetration rate of meloxicam. The penetration rates were significantly increased by about 70–593 fold and the lag times were shortened from 7.92 to 0.17 hr by enhancer incorporation. Among these terpenes, menthol showed the greatest effect. The result showed that the response surface methodology and multiple response optimization utilizing a polynomial equation can be successfully used to obtain the optimal mixed-solvent system and design a meloxicam hydrogel.
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