In-vitro evaluation of meloxicam permeation using response surface methodology

The influences of combination of different mechanisms of penetration enhancers (such as azone, sodium lauryl sulfate and menthol) on the percutaneous absorption of meloxicam formulations throughh rat skin were investigated using uniform deign and response surface methodology. The uniform design was applied to prepare systematic model formulations which were composed of three formulation factors: Azone (x1), sodium lauryl sulfate (x2), and menthol (x3). The result showed that azone had the highest potential influence on the penetration absorption of meloxicam, followed by sodium lauryl sulfate and menthol. With zero-order delivery, the required flux of meloxicam gel to maintain a therapeutic concentration was about 400 μg/hr/cm2. The result showed that the optimal addition concentration of azone at 4% to 6% could be obtained at high penetration rate and short lag time of meloxicam gel. It was shown that as the concentration of sodium lauryl sulfate increased from 0% to 12% the flux and cumulative amount at 48 hr increased and lag time decreased. On the other hand, menthol had the effect of a shorter lag time. To validate the predictive ability of the hypothesized model, the predicted formulations were prepared and penetration experiments were performed. The predicted formulations were developed for the transdermal drug delivery system.