X-Ray Microtomography Analysis of Intragranular Drug Migration During Fluidized Bed and Oven Tray Drying

During the drying process of a wet granulate, water-soluble compounds can migrate to the outer layers of the granule with the evaporating solvent. This migration can affect structural and mechanical characteristics of the granules as the solute accumulates on the granule's outer crust. The objective of this study was to compare the effect of the fluidized bed and oven tray at different drying temperatures on the characteristics of intragranular migration. The extent of migration and the migration effect on granule structure and granule strength were investigated using light microscopy and computerized X-ray microtomography, in both qualitative and quantitative terms. In addition, a mechanical tester was used to assess granule strength and granule failure type. Multivariate analysis of variance with a follow-up discriminant analysis was conducted to investigate the effect of the drying method and the drying temperature on the granule structure. There were significant differences in the intragranular distribution of water-soluble compound as well as in the granule structures and mechanical properties between the drying methods, where drying temperature had only a marginal effect. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association