Design, Development and Evaluation of Metoprolol Succinate and Hydrochlorothiazide Bilayer Tablets

Lowering elevated blood pressure (BP) with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events. Due to the marked variability in an individual patient’s BP response and low response rates with monotherapy, expert groups such as Joint National Committee (JNC) emphasize the value of combination antihypertensive regimen, usually of different classes, having additive antihypertensive effects. Metoprolol succinate is a Beta – 1selective (cardio selective) adrenoceptor blocking agent formulated to provide sustained release of Metoprolol. Hydrochlorothiazide (HCT) is a well established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubules. The objective of the current research work is to design and evaluate an oral bilayer tablet containing Metoprolol succinate as sustained release and hydrochlorothiazide as immediate release layer. Sustained layer were prepared by wet granulation method using different grades of HPMC (HPMCK4M and HPMC K100M) as hydrophilic polymers and immediate release layer prepared by direct compression. The tablets were evaluated for physicochemical parameters. In vitro release studies were carried out using USP (type II) paddle apparatus. Combination of polymers namely HPMCK4M and HPMC K100M showed a controlled release of drug from sustained layer. The in vitro release profiles of drug from sustained release layer could be best expressed by Korsmeyer peppas equation as the plots showed high linearity (R = 0.999). The present study concluded that bilayer tablets of Metoprolol succinate and Hydrochlorothiazide as an alternative to the conventional dosage form.