Direct Tableting on a Continuous Manufacturing Line—Impact of Mixing Parameters, Material Densities, and Drug Load on Subsequent Process Parameters and Tablet Quality
Feb. 17, 2023, midnight
Marius J. Kreiser
Karl G. Wagner
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In recent years, continuous manufacturing (CM) of solid oral dosage forms has gained significant attention, emerging as a leading technology in the pharmaceutical industry. A model has been formulated based on data derived from two design of experiments (DoEs), exploring the influence of mixer process parameters—throughput (THR), hold-up mass (HUM), impeller speed (IMP), and input raw material bulk density (BD)—on the continuous process and the resulting drug product. These statistical models provide equations describing interactions among process parameters for optimization purposes.
Optimal process conditions for the exit valve opening width (EV) at the bottom of the continuous mixer (CMT) were identified as a combination of high throughput (30 kg/h) and low impeller speed (300 rpm). Attributes such as the apparent bulk density of the blend (BD) within the process, fill depth (FD), and tensile strength (TS) were primarily influenced by the input bulk density (BD) of the tableting mixture, underscoring the significance of material properties in the continuous manufacturing process.
The apparent bulk density, aside from its dependency on input bulk density, exhibited equal dependence on THR and IMP in opposite deflections. However, the impact of process parameters (THR and IMP) on apparent BD was found to be minor compared to the input bulk density. FD was predominantly affected by THR ahead of IMP, while TS was influenced by both IMP and THR to a similar extent but in opposite deflections. Additionally, a simplified linear model for estimating input bulk density demonstrated satisfactory predictive accuracy when incorporated into the derived statistical model equations.