Development of Sustained Release Pellets of Galantamine HBr by Extrusion Spheronization Technique Incorporating Risk based QbD Approach

Objective: The present research aims to integrate the concept of quality by design (QbD) to develop galantamine HBr modified release pellets and to scrutinize the critical factors that can affect the quality of the pellets prepared by extrusion spheronization technique. Materials and Methods: Modified release pellets of galantamine HBr were prepared using Compritol 888 ATO and ethyl cellulose (EC) as release retardants. Avicel pH 101 was selected as an extruder aid. Before converting the wet extrudates in pellets, pregelatinized starch was sprinkled on them to improve the physical properties of the pellets. Qualitative risk analysis was performed to screen and identify the significant factors using Failure Mode Effect Analysis (FMEA) model. Central composite design was adopted to optimize the formulation. Concentration of Compritol and concentration of ethyl cellulose were selected as independent factors and drug release at 2, 6, and 10 h were selected as dependent variables. The pellets were evaluated for size, shape, flow, % yield, % friability and drug content. Results and Discussion: Concentration of Compritol and concentration of EC were found to be critical factors from FMEA model. All the batches of central composite design showed excellent flowability, spherical shape, desired size, yield, friability and drug content. Multiple linear regression analysis and analysis of variance were performed to identify the effect of independent variables on different responses. Design space was generated from the data. In vivo plasma concentration time profile was predicted from in vitro data. Conclusion: Concentration of Compritol and EC were found to be significant for the development of modified release pellets. Innovative finding of the present research is to explore the potential use of pregelatinized starch as a dry binder in the post wet extrusion step.