Formulation Optimization of Diltiazem HCl Matrix Tablets Containing Modified Guar Gum using a Central Composite Design

Abstract

The purpose of this study was to develop sustained-release tablets of diltiazem HCl using alkali-treated guar gum as a hydrophilic matrixing agent. The effect of NaOH concentration on swelling of modified guar gum was more pronounced than that of time and temperature. The tablets of diltiazem HCl, containing either untreated or modified guar gum, were compared in terms of drug dissolution, matrix erosion and hydration. The drug release profile of the tablets containing untreated guar gum showed a tailing effect in the terminal phase, which was not observed in the tablets containing modified guar gum. Poor correlation was found between erosion and drug dissolution. The tablets swelled considerably during the hydration study. A uniform precision rotatable central composite design was used to investigate the influence of the amount of diltiazem HCl, modified guar gum and succinic acid on in-vitro drug dissolution. Interactive polynomial models were evolved for the time required for 63.2(t63.2) and 80% (t80) drug release. Response surface plots were generated to show the effect of formulation variables on t63.2. A polynomial equation was also derived for prediction of the drug release profile. An ideal formulation was selected by applying various constraints such as t63.2, t80 and percentage drug released in 60, 360, 540 and 720 min. The kinetics of drug release fitted the Weibull model. It was concluded that modified guar gum could be used as an economical hydrophilic matrixing agent for the formulation of sustained-release tablets of diltiazem HCl.