Verapamil Hydrochloride

The aim of the present study was to develop sustained release formulation of Verapamil Hydrochloride to maintain constant therapeutic levels of the drug for over 12 hrs. Various grades of HPMC polymers, Guar gum and Xanthan gum were employed as polymers. Verapamil Hydrochloride dose was fixed as 120 mg. Total weight of the tablet was considered as 400 mg. Polymers were used in the concentration of 60, 120 and 180 mg concentration. All the formulations were passed various physicochemical evaluation parameters and they were found to be within limits. Whereas from the dissolution studies it was evident that the formulation (F6) showed better and desired drug release pattern i.e., 96.10 % in  12 hours containing Guar gum polymer in the concentration of 180mg . It followed zero order release kinetics. For the optimized formulation alcohol effect has been studied by using various concentrations of alcohol in dissolution medium. As the concentration of alcohol increases the sustained action of polymer was decreased. Hence it was concluded that alcohol has significant effect on drug release pattern.

Verapamil hydrochloride has a short half-life 2.8 to 7.4 hours, a narrow absorption window and is mainly absorbed in proximal areas of GIT. The present investigation aimed to formulate a floating drug delivery system of Verapamil Hydrochloride by Quality by design approach. In risk assessment, the effects of process and formulation variables on particle drug release and floating lag time were investigated. Design of experiments (DoE) and multivariate data analysis were used to identify important process and formulation parameters. A 22 factorial design in replicate was employed to produce controlled release floating tablet. The effect of critical formulation variables i.e. levels of HPMC K15M and gas generating agent (i. e. Sodium bicarbonate and citric acid) on % Drug release after 12 hr (% DRel12) and floating lag time (FLT) were analyzed. Verapamil HCl tablets were evaluated for hardness, friability, weight variation, drug content, floating behavior and drug release studies were conducted in 0.1 N HCl (pH 1.2) at 37 ± 0.5OC. The tablets showed acceptable physicochemical properties. The two independent variables studied exhibited a significant influence (P < 0.05) on % DR 12 Hr and FLT. Numerical and graphical optimization technique employing design space approach was used to develop a new formulation by setting constrains on the dependent and independent variables. The experimental values of % DR 12 Hr and FLT for optimized batch were found to be in close agreement with those predicted by mathematical model. Experimental values obtained from the optimized formulations were in both cases close to the predicted values, thus confirming the validity of the generated mathematical model. These results demonstrated the effectiveness of the proposed floating tablet, as well as the usefulness of the QbD approach for the development of Verapamil floating tablet with optimized properties.

  Gastro retentive drug delivery system has been widely used to prolong retention of dosage forms in stomach. Amongst the various approaches, the Raft formulation offers sustained drug release as well as prolonged gastric retention, along with the added advantage of liquid oral dosage form. The present study was an attempt to formulate and evaluate Raft forming floating drug delivery system for Verapamil Hydrochloride which undergoes pH dependent sol-gel transition at gastric pH; thereby prolonging the retention of the system in stomach. Gellan gum (Gelrite®) was employed as gelling agent whose gelation is triggered by source of Ca2+ ions in the form of Calcium Carbonate. The evaluation was carried out for In Vitro parameters and the results substantiated that the optimized formulation revealed excellent floating characteristics and gastric retention.