Development of Extended Zero-Order Release Gliclazide Tablets by Central Composite Design

Abstract

The purpose of this study was to develop an extended release tablet formulation containing gliclazide as a model drug by optimization technique. A central composite design was employed with pH-dependent matrix forming polymers like keltone®-HVCR (X₁) and eudragit®-EPO (X₂) as independent variables. Five dependent variables were considered: hardness, percent drug release after 1 hr, percent drug release after 6 hr, diffusion exponent and time required for 50% of drug release. Response surface methodology and multiple response optimization utilizing a quadratic polynomial equation were used to obtain an optimal formulation. The results indicate that Factor X₁ along its interaction with Factor X₂ was found to be significantly affecting the studied response variables. An optimized formulation, containing 8 mg of keltone®-HVCR and 14.10mg of eudragit®-EPO, provides a sufficient hardness (> 4.5 kg/cm²) and optimal release properties. The desirability function was used to optimize the response variables, each having a different target and the observed responses were highly agreed with experimental values. The release kinetics of gliclazide from optimized formulation followed zero-order release pattern. The dissolution profiles of optimized formulation before and after stability studies were evaluated by using similarity factor (f₂) and were found to be similar. The results demonstrate the feasibility of the model in the development of extended release dosage form.

Keywords:

• gliclazide
• extended release tablets
• keltone®-HVCR
• eudragit®-EPO
• central composite design