Implementation of “Quality by Design (QbD)” Approach for the Development of 5-Fluorouracil Loaded Thermosensitive Hydrogel

Background: The purpose of this study was to investigate Quality by Design (QbD) principle for the preparation of hydrogel products to prove both practicability and utility of executing QbD concept to hydrogel based controlled release systems. Product and process understanding will help in decreasing the variability of critical material and process parameters, which give quality product output and reduce the risk. This study includes the identification of the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) from literature or preliminary studies. Methods: To identify and control the variability in process and material attributes, two tools of QbD was utilized, Quality Risk Management (QRM) and Experimental Design. Further, it helps to identify the effect of these attributes on CQAs. Potential risk factors were identified from fishbone diagram and screened by risk assessment and optimized by 3-level 2- factor experimental design with center points in triplicate, to analyze the precision of the target process. This optimized formulation was further characterized by gelling time, gelling temperature, rheological parameters, in-vitro biodegradation and in-vitro drug release. Results: Design space was created using experimental design tool that gives the control space and working within this controlled space reduces all the failure modes below the risk level. Conclusion: In conclusion, QbD approach with QRM tool provides potent and effectual pyramid to enhance the quality into the hydrogel. Keywords: Control strategy, critical quality attributes, critical process parameters, critical material attributes, design space, experimental design, quality risk management, risk criticality assessment.