Formulation and optimization of floating matrix tablets of clarithromycin using simplex lattice design

ABSTRACT

The purpose of the present study was to prepare floating matrix tablets of clarithromycin employing simplex lattice design. Hydroxypropyl methylcellulose [HPMC] and Ethyl Cellulose [EC] were used as matrix forming agents; sodium bicarbonate and citric acid as effervescence producing agents. Simplex lattice design was used as optimization technique employing three independent formulation variables viz. concentration of HPMC [X[1]], Citric Acid [X[2]], EC [X[3]] whereas floating lag time, t[50%], t[90%], and MDT [Mean Dissolution Time] were the response [dependent] variables. Seven formulations [F1-F7] were prepared and evaluated for dissolution studies, floating characteristics, weight variation, hardness, thickness, friability.t[50%] of the formulations was found to be ranging from 317 +/- 2.54 to 522 +/- 2.39 minutes. The t[90%] and MDT of the tablets were found to be ranging between 659.65 +/- 1.89 to 967.35 +/- 1.67 minutes and 527.20 +/- 1.22 to 846.78 +/- 2.61 minutes respectively. Total floating time of the formulations was more than 12 hours and the drug content was in the range of 98.54 +/- 0.46 to 99.92 +/- 0.32. The amount of both HPMC and EC were found to play a dominating role in controlling the release of the drug from the formulation whereas ratios of sodium bicarbonate and citric acid were showing significant effect on the floating lag time. The release exponent [n] from Korsmeyer-Peppas model was found to be between 0.62 and 0.75 indicating non-Fickian or anomalous drug release behavior from the formulated floating matrix tablets. Simplex lattice design was reported to be an effective optimization technique for optimizing pharmaceutical formulations against desired responses