With the current transformation of the pharmaceutical industry towards continuous manufacturing, there is an inherent need to embrace this concept already during the early stages of drug formulation. Therefore, this research paper investigated the feasibility of using miniaturized forced feeders on a high-speed rotary tablet press with the intention of downscaling the tableting process. Forced feeders with a reduced volume (up to 46% compared to the conventional two-compartment forced feeder) were designed by either sealing one compartment (i.e. R&D1) or lowering of the compartment height (i.e. R&D2). These feed frame designs were thoroughly analysed in combination with two paddle types over a wide range of process-settings (i.e. tableting speed, paddle speed, direction of paddle rotation, overfill-level). A poorly flowing model powder (i.e. MCC 101) was deliberately selected as challenging formulation. Empirical modelling of feed frame R&D1 revealed a positive impact on the die-filling variability when the radial curved cuboid paddles rotated in counterclockwise direction at high paddle speed. Moreover, a strong resemblance between the R&D2 feed frame and the conventional forced feeder was observed during multivariate data analysis, indicating that this miniaturized type could be used during downscaling studies of the conventional tableting process. The potential of this forced feeder was acknowledged by the similar trends in die-filling variability with respect to varying process settings, when a design-of-experiments (DOE) was performing including feed frame type as a qualitative factor. Overall, it was concluded that both types of miniaturized forced feeders can be used on a high-speed rotary tablet press when lower material consumption rates are desired while the R&D2 feed frame bears the highest predictability regarding the die-filling uniformity in the conventional larger two-compartment forced feeder.
- MeSH
- celulosa MeSH
- farmaceutická technologie metody MeSH
- miniaturizace MeSH
- pomocné látky MeSH
- tablety * MeSH
- Publikační typ
- časopisecké články MeSH
Despite the high quantities of tablets produced daily, many tableting processes are still operated at sub-optimal settings and hence lack the necessary flexibility to mitigate for possible process deviations. However, to ensure this flexibility on tableting throughput it is important to select the most robust feed frame design and settings regarding die-filling. In this research study, four paddle designs for a two-compartment forced feeder (equipped with a metering and a feeding paddle wheel) were evaluated at a wide range of process-settings (i.e. tableting speed, paddle speed, overfill level) and feed frame features (i.e. deaeration) for their impact on the die-filling step of a poorly flowing model formulation (i.e. MCC 101) using a quality-by-design approach. No benefit on die-filling was observed when using higher speeds of the metering paddle wheel compared to the feeding paddle wheel, and no convincing arguments were obtained to use the feed frame deaeration opening. Some combinations of paddle design and process-settings significantly increased the risk for inconsistent die-filling (i.e. high tablet weight variability) which can therefore limit the efficiency of the tableting process. The approach used in this study enabled to compare the paddle designs for their die-filling performance in function of varying tableting speeds, eventually resulting in the selection of a feed frame design that is most robust and therefore will provide a uniform die-filling over a wide range of throughputs. Selection of the most robust parameters is an important prerequisite for the ability of using the rotary tablet press as an agile unit-operation.
- MeSH
- celulosa chemie MeSH
- prášky, zásypy, pudry MeSH
- příprava léků přístrojové vybavení MeSH
- tablety * MeSH
- tvrdost MeSH
- Publikační typ
- časopisecké články MeSH
