Pharmaceutical excipients properties and screw feeder performance in continuous processing lines: a Quality by Design (QbD) approach

Santos, Bianca Aloise Maneira Corrêa; Carmo, Flávia Almada do; Schlindwein, Walkiria; Muirhead, Gordon; Rodrigues, Carlos Rangel; Cabral, Lúcio Mendes; Westrup, Julian; Pitt, Kendal

doi:10.1080/03639045.2018.1513024

Cited by 16 publications

(7 citation statements)

References 29 publications

(59 reference statements)

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“…Ratholes in the feed chute were observed for both K15M CR and K100M CR which prevented the refill from being completed. A similar phenomenon was observed in other feeder studies with different materials and equipment (Cartwright et al, 2013;Santos et al, 2018).…”

Section: Liw Feeder Studiessupporting

confidence: 88%

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

Allenspach

Timmins

Lumay

et al. 2021

International Journal of Pharmaceutics

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Minimizing variability in the feeding process is important for continuous manufacturing since materials are fed individually and can impact the final product. This study demonstrates the importance of measuring powder properties and highlights the need to characterize the feeding performance both offline with multiple refills and in the intended configuration for the continuous manufacturing equipment. The standard grade hydroxypropyl methylcellulose (HPMC) had material buildup on the loss-in-weight feeder barrel from triboelectric charging and resulted in more mass flow excursions and failed refills which were not observed with the direct compression grades. The location of the electrostatic buildup changed when the feeder was connected to a hopper instead of feeding offline into a collection bucket. Overall, the direct compression HPMC exhibited better flow which resulted in more accurate loss-in-weight feeding with less excursions from the target mass flow and all refills were completed in the first attempt. The improvements with the direct compression HPMC would be beneficial when running any continuous process (wet granulation, roller compaction, or direct compression) or other processes where loss-in-weight feeding is utilized, such as melt extrusion or twin screw granulation.

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Section: Liw Feeder Studiessupporting

confidence: 88%

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

Allenspach

Timmins

Lumay

et al. 2021

International Journal of Pharmaceutics

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“…Many studies have been conducted under process-relevant gravimetric feeding mode. To gain understanding of the material-feeder interaction, volumetric feeding studies have also been performed [19,21,31,41]. The volumetric feeding performance of the two polyols grades investigated in this study was found to be consistent across all the feeding strategies and process conditions tested and resulted in relatively high levels of mass flow.…”

Section: Effect Of Materials Attributes On Feeding Performancementioning

confidence: 74%

“…The bulk (BD) and tapped (TD) density of the powders were determined using the cylinder method [41] on a Pharma Test PT-TD200 (Pharma Test, Germany), and the derived Hausner ratio (HR) and Carr index (CI) were selected as flowability descriptors.…”

Section: Particle and Bulk Characterizationmentioning

confidence: 99%

Assessment of Tribo-charging and Continuous Feeding Performance of Direct Compression Grades of Isomalt and Mannitol Powders

et al. 2023

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Tribo-charging is often a root cause of mass flow deviations and powder adhesion during continuous feeding. Thus, it may critically impact product quality. In this study, we characterized the volumetric (split- and pre-blend) feeding behavior and process-induced charge of two direct compression grades of polyols, galenIQ™ 721 (G721) for isomalt and PEARLITOL® 200SD (P200SD) for mannitol, under different processing conditions. The feeding mass flow range and variability, hopper end fill level, and powder adhesion were profiled. The feeding-induced tribo-charging was measured using a Faraday cup. Both materials were comprehensively characterized for relevant powder properties, and their tribo-charging was investigated for its dependence on particle size and relative humidity. During split-feeding experiments, G721 showed a comparable feeding performance to P200SD with lower tribo-charging and adhesion to the screw outlet of the feeder. Depending on the processing condition, the charge density of G721 ranged from -0.01 up to -0.39 nC/g, and for P200SD from -3.19 up to -5.99 nC/g. Rather than differences in the particle size distribution of the two materials, their distinct surface and structural characteristics were found as the main factors affecting their tribo-charging. The good feeding performance of both polyol grades was also maintained during pre-blend feeding, where reduced tribo-charging and adhesion propensity was observed for P200SD (decreasing from -5.27 to -0.17 nC/g under the same feeding settings). Here, it is proposed that the mitigation of tribo-charging occurs due to a particle size-driven mechanism. Graphical abstract

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“…Unmilled, milled, and micronized powders were included, as were a range of particle morphologies, including needles. The aim was to have materials both above and below the FFC of 3, which has been shown elsewhere to be a key parameter in determining acceptable performance in LIW feeders 35 . In addition, excipient materials were also chosen and were all expected to have higher FFC's than 3, as demonstrated in previous studies.…”

Section: Selecting Materials and Techniques For The Studymentioning

confidence: 99%

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

et al. 2020

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Purpose: Understanding and predicting the flow of bulk pharmaceutical materials could be key in enabling pharmaceutical manufacturing by continuous direct compression (CDC). This study examines whether, by taking powder and bulk measurements, and using statistical modelling, it would be possible the flow of a range of materials likely to be used in CDC. Methods: More than 100 materials were selected for study, from four pharmaceutical companies. Particle properties were measured by static image analysis, powder surface area and surface energy techniques, and flow by shear cell measurements. The data was then analysed and a range of statistical modelling techniques were used, to build predictive models for flow. Results: Using the results from static image analysis a model could be built which allowed the prediction of likely flow in a shear cell, which can be related to performance in a CDC system. Only a small amount of powder was required for the image analysis. Surface area did not add to the precision of the model, and the available surface energy technique did not correlate with flow. Conclusions: A small sample of powder can be examined by Static image analysis, and this data can be used to give an early read on likely flow of a material in a CDC system or other pharmaceutical process, allowing early intervention (if necessary) to improve the characteristics of a material, early in development.

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Pharmaceutical excipients properties and screw feeder performance in continuous processing lines: a Quality by Design (QbD) approach

Cited by 16 publications

References 29 publications

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

Loss-in-weight feeding, powder flow and electrostatic evaluation for direct compression hydroxypropyl methylcellulose (HPMC) to support continuous manufacturing

Assessment of Tribo-charging and Continuous Feeding Performance of Direct Compression Grades of Isomalt and Mannitol Powders

Demonstration of the Feasibility of Predicting the Flow of Pharmaceutically Relevant Powders from Particle and Bulk Physical Properties

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