Comparison of Single Pot and Multiphase High Shear Wet Granulation Processes Related to Excipient Composition

At present time, industrial production imperatives can require the transposition of a formulation from one equipment to another. In order to evaluate the impact of such a switch on the properties of granules and tablets, investigations were undertaken on formulations manufactured both in a single pot mixer-granulator-dryer (high shear granulator with in situ double jacket vacuum drying) and in a multiphase equipment (high shear granulator/fluid bed dryer). Principal component analysis highlighted the major contribution of the binder ratio on granule size distribution, flow and packing ability whereas the relative ratio of mannitol and lactose, used as fillers, mainly impacted on compressibility and tablet cohesion. In the studied domain, the lubricant ratio did not explain the considered responses. Statistical analysis (comparison of means, analysis of variance and PCA) showed that both processes led to products with similar characteristics which demonstrated the ability of the processes to produce granules with close quality. However, Fielder®/Niro® granule characteristic data were found to be more dispersed, thus demonstrating a higher sensitivity of the multiphase process to formulation changes. Technological properties of granules and tablets were found to be maintained or improved therefore securing the switch from single pot to multiphase equipments. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3761-3775, 2009