Quality by design

The need of the day is to produce the product that meets customer requirements. As pharmaceuticals are related to health care this should be vital part of industry to produce a product such as tablets, capsules, ointments, creams, gels and emulsions etc. with minimum variation satisfying the needs of customer. Customer requirements are translated into ‘Critical to Quality’ (CTQ) characteristics of the products that they are about to produce by the formulation scientists.  As example, hardness, thickness, uniformity of weight, assay, dissolution etc are CTQ characteristics of tablets, Content uniformity, viscosity, density are CTQ characteristics of a gel etc.  There are various sources of variation which can be monitored by the Quality by Design i.e., QbD approach. Process should be monitored and controlled by using statistical process control which includes six sigma approach, process capability and control charts. Some of the more frequently used indices are Cp and Cpk. Cp represents process capability while Cpk is the process capability index which are determined between USL and LSL which signifies upper specification limit and lower specification limit. Cpk of at least 1.33 is desired, and 1.5 is excellent and if there are not more than 3.4 defects per million units, then six sigma is achieved.

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.