Formulation and Evaluation of Controlled Release Matrix Tablets of Labetalol Hydrochloride

INTRODUCTION Controlled release oral dosage forms are in the focus of interest for several reasons. Customer compliance with the trend to simplicity and more comfort of use, the prolonged drug release with more reliable blood levels than those obtained with conventional dosage forms and life-cycle management of existing API’s directed the pharmaceutical development towards sustained release formulations. The basic rationale for controlled drug delivery is to alter the pharmacokinetics and pharmacodynamics of pharmacologically active moieties by using novel drug delivery system or by modifying the molecular structure and /or physiological parameters inherent in a selected route of administration. HPMC and Carbopol are used as matrix materials. The matrix may be tableted by wet granulation tech. Antihypertensive drugs are used for prevention of stroke. Stroke is associated with a wide variety of reasons and hence the presence of adequate amounts of plasma drug levels becomes very necessary for efficient treatment of hypertension. Antihypertensive drugs have short halflives, extensively metabolized in the liver and are highly bound to plasma proteins. Hence if the release of drug is sustained for a longer period of time, will result in efficient management of hypertension.Labetalol hydrochloride is a selective αand nonselective βadrenergic blocking agent.It is used in management of hypertension, alone or in combination with other classes of antihypertensive agents. Labetalol hydrochloride is one of several preferred initial therapies in hypertensive patients with heart failure, post-MI, high coronary disease risk, or diabetes mellitus. It can be used as monotherapy for initial management of uncomplicated hypertension. Labetalol hydrochloride is also effective in controlling blood pressure in pregnant women with moderate to severe hypertension and severe pregnancy-induce hypertension. Labetalol hydrochloride has a dosage of 300 mg twice daily initially. For maintenance, manufacturer recommends a usual dosage of 200–400 mg twice daily. Manufacturer states that some adults with severe hypertension may require up to 1.2 g–2.4 g administered in 2 or 3 divided doses daily. Labetalol hydrochloride is rapidly and almost completely absorbed (i.e., 90– 100%) from the GI tract following oral administration. It undergoes extensive firstpassmetabolism in the liver and/or GI mucosa.Absolute bioavailability is about 25%. Therefore to improve bioavailability and patient compliance in this study attempt has been made to develop a controlledrelease dosage form. MATERIALS AND METHODS Materials Labetalol hydrochloride was obtained as gift sample from aurobindo pharma Pvt. Ltd. Labetalol hydrochloride is used in treatment of hypertension. It has a short half life and undergoes extensive first pass metabolism. In the present study, labetalol hydrochloride 300 mg controlled release matrices were prepared by wet granulation method and invitro drug dissolution studies were performed to find out the drug release rate and patterns. HPMC (K4 M, K15 M ), Eudragit S100,carbopol and their combination were used as rate controlling polymers. Tablets were formulated using different polymer ratios. as In-vitro drug release was carried out using USPType II at 50 rpm in 900 ml of acidic dissolution medium (pH 1.2) for 2 hours, followed by 900 ml alkaline dissolution medium (pH 6.8) upto 12 hours. Mean dissolution time is used to characterize drug release rate from a dosage form and indicates the drug release retarding efficiency of polymer. When HPMC K4 M and HPMC K15 M were used alone as the only retarding polymer, a sustained drug release pattern were not observed while, combination in the matrix almost doubled the time required for releasing the drug. Several kinetic models were applied to the dissolution profiles to determine the drug release kinetics.