OPTIMIZATION OF PANTOPRAZOLE ENTERIC PELLETS COATING PROCESS BY QBD: EFFECT OF COATING PROCESS VARIABLES ON THE INTERMEDIATE QUALITY OF THE PRODUCT AND SCALE UP

摘要

Objective: The aim of this study was to optimize pantoprazole enteric coating process based on Quality by Design (QbD) principle and successful scale up. Methods: The critical process parameters (CPP) were identified based on Failure Mode and Effect Analysis (FMEA) tool. A full factorial design was applied to develop design space and determine control strategy for pantoprazole enteric coating process, have promising yield, assay and reduced process time. The coating process variables studied were air volume (X 1 ), spray rate (X 2 ) and atomization air pressure (X 3 ), versus percentage fines (Y 1 ), percentage agglomerates (Y 2 ) and assay (Y 3 ) as responses. The pellets were coated in Wurster and characterized for assay, dissolution, scanning electron microscopy and loss on drying. Results: When X 2 at low level and X 3 at high level, spray drying increased hence fines increased while X 2 at a high level and X 3 at a low level, agglomeration increased. The optimization performed to decide level of X 2 and X 3 for fines and agglomerated free process. The operating ranges, for robust coating process of desired pellets yield and quality, X 1, X 2 and X 3 were 46-58 CFM, 6-9 g/min and 1.1-1.3 bar respectively. In scale up of pellets, physical and chemical parameters reproduced based on process ran as per scale up factor calculation. Conclusion: It was concluded that a promising pellets coating process was successfully designed using QbD approach and successfully scale upscale up possible based on complete optimization of process variables, understanding of risk associated with variables and implementation of scale-up factor calculation provided by the vendor. Keywords: Wurster, Risk assessment, Design space, Control strategy, FMEA, Scale up, QbD