Metoprolol succinate controlled release multi unit particulate formulation for reconstitution using a risk based QbD approach


The purpose of this work was to develop multi unit particulate formulation using fluid bed processor for the controlled release of Metoprolol succinate and to understand the impact of formulation parameters on the critical quality attributes using a quality-by-design approach. For this, the impact of various formulation parameters on the drug release at 1, 4, 8 and 20 h was investigated. Initial risk assessment was performed with the help of Failure Mode and Effects Analysis tool, to identify the failure modes that had the greatest chance of causing product failure, i.e., not meeting the Quality Target Product Profile. Optimization was done using a two-factor, three-level Face Centered Composite design. The formulation comprising of 65% coating extent and 1: 0.8:: drug: polymer ratio was found to fulfill the requisites of an optimum formulation. In vitro release studies showed that the drug was released from the optimized formulation over a period of 20 h in a controlled release manner. In vivo studies in rabbits revealed that the drug release was controlled for 20 h. The present research highlighted the level of understanding that can be accomplished through a well designed study based on the QbD approach.


Risk assessment by QBD
Initial and final risk assessment by failure mode and effects analysis (FMEA)