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The tendency of powder mixtures to demix due to segregation is a substantial technical concern for manufacturing of pharmaceutical solid dosage forms. In this paper, a methodology for quantifying the maximum potential segregation, as well as predicting the actual, segregation of a powder blend is outlined. The method begins with measurement of the sieve assay profile of the blend. Individual component and overall size segregation indices are defined in terms of overlap integral calculations that characterize the maldistribution of the components among the sieve fractions. This approach has been in use since 2001 at Merck & Co. for multicomponent polydisperse pharmaceutical powder blends and is appropriate for direct compression blends and agglomerated systems, including ordered mixtures. Die-filling performance can be predicted when the individual maldistribution index ( Di ) is combined with blend flowability (gravity-normalized cohesivity) on a regime map. This map strongly confirms that better blend flowability increases segregation realization. The approach permits rational risk assessment for existing product changes and optimization of new formulations. Analysis assumptions are discussed and deemed to be conservative with respect to prediction of demixing. [ABSTRACT FROM AUTHOR]

Predicting structural and flow characteristics of cohesive powder systems is a technical challenge in many powder technology applications. The discrete element method (DEM) is a promising approach to model the mesoscale structure and flow behavior of cohesive granular systems. Advances in experimental techniques such as X-ray computed tomography (XRCT) have enabled characterization of powder systems with sub-micron resolution. Combined with standard bulk powder characterization methods, this technique allows for mesoscopic structural characteristics of cohesive powder systems to be compared directly with DEM simulation. In this study, DEM and XRCT are used to characterize the structural characteristics of two moderately cohesive roughly spherical “model” powders – glass and stearic acid – under loosely poured and tapped consolidated conditions. The DEM simulations are based on a constitutive elasto-plastic model that makes use of the JKR theory to account for cohesive interparticle surface forces. Powder density and mesoscopic void structure obtained from DEM simulation are compared to characterization results obtained from XRCT image analysis. The results show that DEM can accurately predict the extent of tapping induced densification and mesostructure characteristics in cohesive powders, with superior agreement for stearic acid. [ABSTRACT FROM AUTHOR]

The USP Apparatus II is the device commonly used to conduct dissolution testing in the pharmaceutical industry. Despite its widespread use, dissolution testing remains susceptible to significant error and test failures, and limited information is available on the hydrodynamics of this apparatus. In this work, laser-Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were used, respectively, to experimentally map and computationally predict the velocity distribution inside a standard USP Apparatus II under the typical operating conditions mandated by the dissolution test procedure. The flow in the apparatus is strongly dominated by the tangential component of the velocity. Secondary flows consist of an upper and lower recirculation loop in the vertical plane, above and below the impeller, respectively. A low recirculation zone was observed in the lower part of the hemispherical vessel bottom where the tablet dissolution process takes place. The radial and axial velocities in the region just below the impeller were found to be very small. This is the most critical region of the apparatus since the dissolving tablet will likely be at this location during the dissolution test. The velocities in this region change significantly over short distances along the vessel bottom. This implies that small variations in the location of the tablet on the vessel bottom caused by the randomness of the tablet descent through the liquid are likely to result in significantly different velocities and velocity gradients near the tablet. This is likely to introduce variability in the test. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2327–2349, 2007 [ABSTRACT FROM AUTHOR]

The USP Apparatus II is the device commonly used to conduct dissolution testing in the pharmaceutical industry. Despite its widespread use, dissolution testing remains susceptible to significant error and test failures, and limited information is available on the hydrodynamics of this apparatus. In this work, laser-Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were used, respectively, to experimentally map and computationally predict the velocity distribution inside a standard USP Apparatus II under the typical operating conditions mandated by the dissolution test procedure. The flow in the apparatus is strongly dominated by the tangential component of the velocity. Secondary flows consist of an upper and lower recirculation loop in the vertical plane, above and below the impeller, respectively. A low recirculation zone was observed in the lower part of the hemispherical vessel bottom where the tablet dissolution process takes place. The radial and axial velocities in the region just below the impeller were found to be very small. This is the most critical region of the apparatus since the dissolving tablet will likely be at this location during the dissolution test. The velocities in this region change significantly over short distances along the vessel bottom. This implies that small variations in the location of the tablet on the vessel bottom caused by the randomness of the tablet descent through the liquid are likely to result in significantly different velocities and velocity gradients near the tablet. This is likely to introduce variability in the test., ((c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.)