Quality by Design Assisted Formulation Development and In-Vitro Evaluation of Bilayer Tablets of Metoprolol Succinate Extended Release and Chlorthalidone Immediate Release for Hypertension Therapy

Abstract

In this study, an attempt was made to develop Bilayer tablets in which one layer is Modified Release layer of Metoprolol Succinate which is a ẞ1-selective adreno-receptor blocking agent with half life 3-4 hrs. and other layer is Immediate Release layer of an oral antihypertensive and diuretic drug, Chlorthalidone its aqueous solubility is very poor hence its bioavaibility also very low. To improve bioavaibility and solubility by enhancing surface area of Chlorthalidone using size reduction technique by using ball mill and shifting method. Modified release layer was formulated using synthetic HPMC and high molecular weight , cross linked polyacrylic acid polymers at different concentrations four formulations were prepared at different polymer concentration. Formulation of Immediate release layer of Chlorthalidone layer was done using sodium starch glycolate and crosspovidone, four batches were formulated having different polymer concentration. The batches get formulated using factorial design. The tablets are made by using method of direct compression. The developed tablets were evaluated by using different evaluation methods like weight variation, drug content uniformity, and thickness, hardness, friability and in-vitro drug release kinetics of modified release tablets. In all formulations, A4 batch of Metoprolol Succinate shows 24 hrs releases and Chlorthalidone shows good release in 20 min.