Statistical Optimization of Ketoprofen-Eudragit® S100 Coprecipitates to Obtain Controlled-Release Tablets

Abstract

Coprecipitates of ketoprofen and Eudragit® S1OO have been prepared by a recently reported technique and compressed as tablets to release 75 mg of the drug in phosphate buffer (pH 7.2) medium in a 12-hour period. A second-order Box-Behnken design has been employed to optimize the independent variables that include the level of polymer Eudragit® S100 used, the level of diluent lactose used, and the applied compressional pressure. The design included a total of 15 experiments for the three variables at three levels each. Tablets containing 75 mg of ketoprofen were compressed according to the design. Dissolution experiments were run by the USP basket method at 100 rpm. Dissolution halftime (t₅₀) was recorded from the plot of cumulative percent of ketoprofen dissolved as a function of time. Hardness and thickness of the tablets were also recorded. A mathematical relationship and response surface plots were generated to determine the relationship between t₅₀ and the independent variables with constraints on the hardness and the thickness. Levels of the independent variables were predicted to obtain the optimum response. The optimization procedure predicted a t₅₀, of 4.81 hours, hardness of 18 kg, and thickness of 0.41 cm when the levels of polymer, diluent, and compressional pressure were 22.86%, 36.92 mg. and 0.97 tons respectively. New formulations that were made accordingly yielded t₅₀, values that were very close to the predicted values.