The effect of material properties and process parameters on die filling at varying throughputs: A PLS-model-based analysis.

When tablets are manufactured on a rotary tablet press and the throughput is increased, it leads to changes in powder dynamics during die filling due to formulation characteristics and changing powder flow in the feed frame. This may result, a.o. in increased tablet weight variability, poorer content uniformity, capping and lamination. This research focuses on explaining the die filling performance depending on material properties and process settings, including throughput for small and large tablets. It was concluded that throughput had a negative impact on die filling variability, which is related to reduced residence time and lower fill fraction of the feed frame and dies. Furthermore, the die filling mechanism was inherently different for large tablets in comparison to small tablets. Higher die filling consistency was observed for dense, less porous, less compressible and better flowing powders. As a result of this work, a model was developed to predict the impact of formulation properties and process settings on die filling variability and its dependency on changes in throughput. This model will benefit formulation development at an early stage when active ingredient availability may be challenging as it will avoid the need to conduct experiments at high throughputs.

Elucidation of the powder flow pattern in a twin-screw LIW-feeder for various refill regimes.

The importance of residence time distribution modeling is acknowledged as a tool for enabling material tracking and control within a continuous manufacturing line in order to safeguard both product quality and production efficiency. One of the first unit-operations into a continuous direct compression line (i.e. CDC-line) worthwhile doing extensive RTD-analysis upon are the LIW-feeders since they dose the ingredients in a controlled way following the label claim and hence can directly influence critical quality attributes like content uniformity. An NIR measurement method was developed determining the RTD of selected powders at specific feeder settings. Step-change experiments using sodium saccharin as a tracer were conducted. In order to gain and in depth understanding of the material flow, spatial samples throughout the hopper were taken at predefined timepoints during the step change experiments. This revealed the presence of a bypass trajectory along the edges of the agitator, while in the center of the agitator an inner mixing volume in which the tracer concentration lags behind seemed to be present. Finally, a model based on a plug flow and continuous stirred tank reactor was evaluated. The fitted model was not able to capture this complex flow behavior and shows the need for an extended compartmental model distinguishing between a bypass trajectory formed by the agitator and an inner mixing volume.

Ethnic disparities and morbidity in the Province of Antwerp, Belgium.

OBJECTIVE: This study aims to identify geographical disparities in perinatal mortality and morbidity in the province of Antwerp, Belgium. We performed a retrospective cohort study from an existing database. Data included from 1 January , 2000 to 31 December, 2009 and including all deliveries in the Province of Antwerp, Belgium. Collected outcome measures : fetal death, early and late neonatal death, preterm birth, low birth weight. Outcomes were analyzed according to postal code of the pregnant women's address. RESULTS: A total of 167.246 deliveries in sixty postal codes were analyzed and statistically significant differences (p<0.001) between postal codes for all outcome measures except for early and late neonatal death were detected. Generally postal codes tend to have either high or low prevalences for all perinatal outcomes and two postal code zones had a significantly worse perinatal outcome on all fields. Major differences in perinatal outcome exist within the well-defined area of the relatively small province of Antwerp, Belgium. CONCLUSION: Perinatal outcome is strongly influenced by maternal postal code even within a relatively affluent European region demonstrating persistent health inequalities and suggesting further research is necessary to explain these differences and create interventions to diminish inequalities.