Design and In-vitro Evaluation of Indapamide Sustained Release Tablet Using Methocel K15 Mcr and Methocel K100m Lvcr

Indapamide, a low-dose thiazide-type diuretic, is used for the treatment of essential hypertension. In this study, we developed an indapamide sustained release formulation using Methocel K15M CR and Methocel K100M LVCR, starch 1500, talc and magnesium stearate considering technical feasibility and performed a comparative study with the release pattern. The tablets showed sustained release curves at pH 6.8 phosphate buffer for up to 12 h. The granules showed satisfactory flow properties, compressibility index and drug content etc. All the tablets complied with pharmacopoeial specifications. The results of dissolution studies indicated that the formulations F-6 and F-8 could extend the drug release up to 12 h. The data obtained from the dissolution profiles were compared in the light of different kinetics models and the regression coefficients were also compared. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport, which was only dependent on the type and amount of polymer used. The drug release followed both diffusion and erosion mechanism in all cases. This study explored the optimum concentration and effect of polymer(s) on Indapamide release pattern from the tablet matrix for 12 h period. INTRODUCTION: Indapamide, a thiazide-type diuretic, is a widely used antihypertensive agent. Numerous randomized controlled studies have shown its antihypertensive efficacy in the immediate-release (IR) formulation at the dosage of 2.5 mg/day. In accordance with the current recommendations, a sustainedrelease (SR), lowdose formulation (Indapamide SR 1.5 mg) was developed with the objective of achieving an optimal efficacy/ acceptability ratio . Indapamide free base is practically insoluble in water (0. 75 mg/L) and thus poorly absorbed from the gastro-intestinal tract. It exhibits poor absolute bioavailability of 30-40% . Half life of Indapamide is 14-18 h . It’s very poor aqueous solubility indicates that its absorption is dissolution rate-limited which might result in irregular and delayed absorption. During the past 30 years, as expenses and complications involved in marketing new drug molecules have increased with concomitant recognition of therapeutic advantages of controlled drug delivery, greater attention has been focused on the development of controlled release drug delivery systems (CRDDS). The goal in designing CRDDS is to reduce the frequency of dosing or to increase the effectiveness of the drug by localization at the site of action reducing the dose required or providing uniform drug delivery . Correspondence to Author: