(274g) Understanding the Impact of Feedframe Design and Process Parameters on the Die-Filling Step of the Tableting Process

Authors: 
Grymonpré, W., Ghent University
Vanhoorne, V., Ghent University
Van Snick, B., Ghent University
De Beer, T., Ghent University
Remon, J. P., Ghent University
Vervaet, C., Ghent University
Powder compression on rotary tablet presses is widespread in various industries and for pharmaceuticals over 80 % of all oral dosage formulations are manufactured as tablets. The ease of tablet manufacturing combined with a high economic efficiency and patient compliance all contribute to the prominent role of tablets as pharmaceutical oral dosage form. With the concept of continuous processing gaining momentum in pharmaceutical manufacturing, a thorough understanding of how process and formulation parameters impact the critical quality attributes (CQA) of the end product is more than ever required. Regarding tableting processes, consistent die-filling is a crucial control variable since this will impact the final product quality (e.g. drug content and tablet weight). Although a wide range of feedframe designs is available in terms of paddle-type, chamber height, powder-flow ‘enhancers’ and feedframe aeration, there is limited knowledge on which specific feedframe design is the most appropriate for a specific formulation in order to obtain consistent die filling during tabletting.

The aim of this study is to investigate the impact of feedframe design and tableting process parameters on the die-filling step and other critical quality attributes (e.g. tablet tensile strength). The knowledge gained via this study will contribute to a rational selection of the feedframe design and tabletting settings in function of the formulation characteristics. Different paddle-types were selected based on their prevalence in the pharmaceutical industry and these were implemented in a standard feedframe consisting of 2 paddle wheels, whereby the feeding wheel had 8 paddles and the recovery wheel 12 paddles. The following 4 feedframe designs were evaluated: curved paddles, straight paddles, thin cylindrical paddles with varying height in the paddle wheel and curved paddle-wheels with lower thickness and a ‘scraper’, together with the possibility of aeration (present or not). An experimental design with 48 runs including 4x2 centerpoints for each paddle-type was conducted on a fully instrumented rotary tablet press (Modul P, GEA Pharma systems) with an additional fill-level sensor mounted on the feeding-tube which ensured a constant powder volume above the feedframe throughout all experiments. Paddle speed (15 - 100 rpm), the ratio of paddle speed 1 (i.e. feeding wheel) over paddle speed 2 (i.e. recovery wheel)(1-1.4), turret speed (10-100 rpm) and overfill-level (0-4 mm) were varied in the DOE as process parameters.

Experiments were performed at a bottom punch position generating a main compression force (15 kN), with a fixed pre-compression displacement (0.5 mm). Steady state of the tablet press was determined by monitoring the tablet mass flow signal on a catch scale. Each experimental run was performed on an empty and cleaned feedframe. After reaching steady state, tablets were sampled at different time points. The sampling duration (required to sample 20 tablets per time point) and sampling interval depended on the turret speed: a 20s sampling duration with an 80s interval at 10 rpm compared to a sampling duration of 2s with an 8s interval at 100 rpm. Tablets were analysed on their weight, tablet dimensions and hardness using a combitester (Pharmatron Smarttest 50), and the pooled mean and pooled relative standard deviation were calculated for tablet weight, tablet tensile strength and tablet porosity as responses. Additionally, the time needed to reach steady state conditions for each experimental run was calculated and the displacement signals on the pre-compression were monitored to evaluate fluctuations in the tablet weight variation. With respect to the latter, main compression forces were also recorded. Based on a PCA analysis of fillers and API’s, microcrystalline cellulose (Vivapur 101) was initially selected as poorly flowing formulation for performing the experiments.

Overall, feedframe design affected the die filling and consequently the mean tablet weight: significantly higher tablet weights were obtained using straight paddles, while the feedframe with ‘scraper’ and lowered curved paddles resulted in significantly lower tablet weights. At some process settings with the latter paddle design, feedframe obstruction occurred due to intensive compaction inside the feedframe. However, no significant influence on the tablet weight variability was detected, indicating that the consistency of die filling seemed guaranteed for each paddle type, specifically since no interaction was observed between paddle type and overfill-level for RSD on tablet weight. The process parameters strongly impacted the tablet weight and weight variability: (a) higher turret speeds resulted in significantly lower mean tablet weight (i.e. less die-filling) and a higher tablet weight variability, (b) more overfill resulted in a higher tablet weight without an effect on tablet weight variability, (c) paddle speed 1 had a similar impact as the overfill-level on the mean tablet weight at higher paddle speeds, yielding a higher tablet weights and lower variability indicative of a more consistent die-filling at higher paddle speed 1 (i.e. feeding wheel) for this formulation. Similar trends were observed when investigating the tablet tensile strengths at each experimental run for this formulation.

The developed experimental design will be repeated with other powder formulations with varying density and flow behavior in order to investigate the robustness of this study towards other formulations. As a result, this research study will contribute to an improved approach for the set-up of future experimental tableting studies.