Revisiting strain rate sensitivity: the role of feed frame-induced lubrication in tablet tensile strength loss during scale-up

Tensile strength loss during scale-up is commonly attributed to strain rate sensitivity, where shorter dwell times are assumed to weaken tablets. Since compression speed and feed frame paddle speed are typically increased together in rotary presses, decoupling their individual impact on tensile strength remains challenging. This study decoupled their impact using a compaction simulator. Materials with different deformation behaviours were studied. Tablets for each material were compressed at two dwell times (lab- and industrial-scale) across different feed frame speeds. Matched in-die porosity was maintained for each material across all conditions to ensure similar in-die densification, and a machine-independent porosity-tensile strength approach was used for analysis. In unlubricated excipients (with and without die-wall lubrication), reducing dwell time from 150 to 15ms showed no reduction in tensile strength; however, hard-brittle dibasic calcium phosphate showed a slight increase. Upon internal lubrication with different magnesium stearate loads, only starch showed a reduction in tensile strength, driven by lubrication and increased elastic recovery at shorter dwell time. Unexpectedly, feed-frame shear at a fixed 1% lubrication load resulted in greater strength loss than increasing lubrication loads for viscoelastic, plastic, and brittle materials. This study reveals that dwell time effects were limited, with only lubricated starch showing a reduction, whereas feed frame shear induced lubrication plays a major role in tensile strength loss during scale-up. These findings enable formulators to implement feed frame focused strategies that maintain tensile strength and support reliable scale-up.

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Publication Details

Journal
International Journal of Pharmaceutics
Published
2026-04-21
DOI
https://doi.org/10.1016/j.ijpharm.2026.126867
Primary Topic
Drug Solubulity and Delivery Systems
Type
article
Field-Weighted Citation Impact
0.00

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article

Revisiting strain rate sensitivity: the role of feed frame-induced lubrication in tablet tensile strength loss during scale-up

Kendal Pitt, Musab Osman, Daniel Markl, Catherine Yates et al.
International Journal of Pharmaceutics
Drug Solubulity and Delivery Systems
article

Revisiting strain rate sensitivity: the role of feed frame-induced lubrication in tablet tensile strength loss during scale-up

Kendal Pitt, Musab Osman, Daniel Markl, Catherine Yates, Pratik P. Upadhyay, Gavin Reynolds, John Robertson
article en

Abstract

Tensile strength loss during scale-up is commonly attributed to strain rate sensitivity, where shorter dwell times are assumed to weaken tablets. Since compression speed and feed frame paddle speed are typically increased together in rotary presses, decoupling their individual impact on tensile strength remains challenging. This study decoupled their impact using a compaction simulator. Materials with different deformation behaviours were studied. Tablets for each material were compressed at two dwell times (lab- and industrial-scale) across different feed frame speeds. Matched in-die porosity was maintained for each material across all conditions to ensure similar in-die densification, and a machine-independent porosity-tensile strength approach was used for analysis. In unlubricated excipients (with and without die-wall lubrication), reducing dwell time from 150 to 15ms showed no reduction in tensile strength; however, hard-brittle dibasic calcium phosphate showed a slight increase. Upon internal lubrication with different magnesium stearate loads, only starch showed a reduction in tensile strength, driven by lubrication and increased elastic recovery at shorter dwell time. Unexpectedly, feed-frame shear at a fixed 1% lubrication load resulted in greater strength loss than increasing lubrication loads for viscoelastic, plastic, and brittle materials. This study reveals that dwell time effects were limited, with only lubricated starch showing a reduction, whereas feed frame shear induced lubrication plays a major role in tensile strength loss during scale-up. These findings enable formulators to implement feed frame focused strategies that maintain tensile strength and support reliable scale-up.

International Journal of PharmaceuticsVol. 697
University of Strathclyde (GB), AstraZeneca (Netherlands) (NL), AstraZeneca (Singapore) (SG), Montagu Hospital (GB), AstraZeneca (Poland) (PL)
AstraZeneca, Engineering and Physical Sciences Research Council
Affordable and clean energy
Openalex Percentile: Top 22%
Drug Solubulity and Delivery Systems
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