A priori performance prediction in pharmaceutical wet granulation: Testing the applicability of the nucleation regime map to a formulation with a broad size distribution and dry binder addition

摘要: Abstract In this study, Hapgood's nucleation regime map ( Hapgood et al., 2003 ) was tested for a formulation that consists of an active pharmaceutical ingredient (API) broad size distribution and fine dry binder. Gabapentin used as the API hydroxypropyl cellulose (HPC) binder with deionized water liquid The granulated in 6 l Diosna high shear granulator. effect addition method (spray, dripping), rate (29–245 g/min), total content (2, 4 10%), impeller speed (250 500 rpm) on granule lump formation were investigated. Standard methods successfully to characterize process parameters (spray drop size, spray geometry powder surface velocity) calculating dimensionless flux. However, had very strong penetration time could not be predicted from simple capillary flow considerations. This is most likely due preferential into pores related particles subsequent partial softening dissolution For systems containing or other amorphous powders, it recommended measured directly blended then scaled during spraying. Using these approaches key groups (dimensionless flux time), predict priori conditions quality by span distribution, both before after wet massing range studied. Wider distributions higher amount lumps obtained moving intermediate mechanical dispersion regime. Addition dripping mode gave broadest ungranulated fines highest percentage compared spraying mode. narrowest lowest lumps. effects complex. At 2% content, increasing adding caused some breakage production fines. contents, less clear, balance between increased consolidation growth. Nevertheless, work has demonstrated complex formulations addition, final still depends strongly homogeneity initial which well analysis.