QbD Based Approach to Design Controlled Strategy for Wet Granulation Method Using Plackett Burman Design-Case Study

Objective: The objective of present work describes developing controlled strategy for wet granulation process by identifying critical process parameters and study was done using DoE in support of Quality by Design (QbD). Material and method: The manufacturing process involves wet granulation process, fluid bed drying, milling, blending, Lubrication, compression and coating. For wet granulation process identified critical process parameters were studies using, the Plackett-Burman factorial design to study four factors at two levels. The DOE was generated and analyzed using Design expert 8 software. Results and discussion: Total 12 trails and were conducted from RUN 1-12. All trials physical properties (bulk and tapped densities), tablet parameters and dissolution profile of the tablets were evaluated. Based on the results, it can be concluded that none of the CPP's have very significant effect on dissolution but impeller speed and wet massing time showed significant effect on disintegration time. At lower level of impeller speed and binder addition rate, higher level of wet massing time model demonstrated higher release profile. Conclusion: Understanding of manufacturing process is of key importance to successful implementation of QbD approach. Using a Design of Experiments approach (Plackett Burman design), the range of operation for the critical process parameters, including the impeller RPM, the rate of water addition, mixing time and the kneading time range were proposed and established control strategy. Operational ranges of critical parameters should be optimized in order to produce quality product in a repeatable manner. Process outcomes within the spec limits indicate a lack of CPPs. Further these categorical variables were identified for use in registration and validation batch manufacture.