Formulation and Evaluation of Hydrodynamically Balanced System for Verapamil Hydrochloride- Gastro Retentive Approach

Objective: The aim of present investigation was to develop HBS system (sustained release) for Verapamil HCl used for the treatment of hypertension. The drug delivery system was designed to retain the system in stomach so that increase in absorption of drug and decrease in dosing interval. Methodology: Single unit capsules were filled with weighed mixture of Verapamil HCl and polymers such as HPMC K15M, sodium alginate and magnesium stearate. Results: The release profile and retention of capsule depending upon the amount of HPMC K15M and sodium alginate concentration. Optimization was done using 32 factorial design considering two independent factors at three levels. Data was evaluated statistically by Stat Ease Design Expert 8.0.1 software. The optimized batch F9 gave drug release at 12 h 65.27±0.35 and at 24 h 92.39±0.21 which consisted of 35% HPMC K15M and 30% Sodium alginate. Conclusion: The Hydrodynamically balanced system of Verapamil HCl was achieved which can increase the gastric residence time as well as bioavailability and thereby showing increased therapeutic efficacy. Keyword: Hydrodynamically balanced system, HPMC K15M, Sodium alginate, 32 factorial design. INTRODUCTION Until now numerous oral controlled drug delivery systems have been developed to prolong drug release. The crucial point in this respect is that the drug has to be absorbed well throughout the whole gastrointestinal tract. For drugs with a narrow absorption window in the GIT or acting locally in the stomach, the challenging task is not only to prolong drug release but the retention of the dosage form in the upper gastrointestinal tract. Such dosage form having density less than that of the gastric fluid floats on the gastric juice for an extended period of time while slowly releasing the drug. [1] In gastro retentive delivery system there is two approaches one is effervescent drug delivery system and another one is non effervescent delivery system i.e. hydrodynamically balanced system. The most commonly used excipients in non effervescent FDDS are gel-forming or highly swellable cellulose type hydrocolloids, polysaccharides, and matrix forming polymers such as polycarbonate, polyacrylate, polymethacrylate and polystyrene.[2] One of the approaches to the formulation of such floating dosage forms involves intimate mixing of drug with a gel-forming hydrocolloid, which swells in contact with gastric fluid after oral administration and maintains a relative integrity of shape and a bulk density of less than unity within the outer gelatinous barrier. The air trapped by the swollen polymer confers buoyancy to these dosage forms. In addition, the gel structure acts as a reservoir for sustained drug release since the drug is slowly released by a controlled diffusion through the gelatinous barrier. [3,4] The need for gastro retentive dosage forms (GRDFs) has led to extensive efforts in both academics and industry towards the development of such drug delivery systems. Fig. 1: Hydrodynamically balanced system Verapamil is an inhibitor of calcium ion influx (slow calcium channel blocker or calcium entry blocker) and causes dose-dependent inhibition of the transmembrane influx of calcium ions into muscle cell via the ‘L’ channel it is stable in acidic pH, has a narrow therapeutic absorption window in the GI tract. [5,6] So verapamil hydrochloride meeting the criteria for selection as the drug candidate to be formulated as a hydrodynamically balanced system. The objective of present study was to formulate floating capsules of Verapamil HCl to deliver the drug continuously with set limits of dissolution profile and minimum floating time of 24 h. MATERIALS AND METHODS