Optimization of Extrusion and Sphenronization Parameters for Tolterodine Tartrate Pellets by Design of Experiment (DoE)

Objective The purpose of this indicative DoE is the optimization of Screw Speed and Sphenronization Speed which may impact the final physical and chemical parameters of pellets such as aspect ratio/sphericity, PSD and dissolution which are pre-requisite for further extended release coating on immediate release pellets. From the risk assessment and Pre DoE, Aspect Ratio, Dissolution at 30 min and PSD were identified as critical quality attributes which may be potentially influenced by the factors s4ch as Screw Speed and Sphenronization Speed and their respective levels. Methods Immediate release pellets of tolterodine were prepared and optimized by employing extrusion spheronization process. The experimental ranges chosen were based on the development experience and prior knowledge. Since the aim of DoE was to assess the impact of factors that would affect the product critical quality attributes (CQAs), a central composite design was chosen. Results The optimized process parameters exhibited required dissolution, PSD and aspect ratio of immediate release pellets which are further required for successful extended release coating. DoE statistical analysis demonstrated the impacts of all factors (in the studied range) on the responses studied. Based on the observation suggested model for PSD below # 25 was Linear, for PSD above # 20-25 its Quadratic, for aspect ratio its Quadratic and for response Dissolution at 30 min its Quadratic Conclusion Based on the statistical analysis and considering the scientific rational product performance, it can be concluded that the Factor A (Screw Speed) and Factor B (Spheronization Speed) were the significant factors which had impact on the response dissolution, aspect ratio and PSD.