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Investigating the effects of temperature on pharmaceutical tablet compression
Date
2025
Abstract
Tablet compaction is a critical process in pharmaceutical manufacturing, in which heat arises by friction between powder particles, interactions with the die wall, tableting instruments, elastic and plastic deformation, and fragmentation of particles. Temperatures can often exceed 50 °C, with literature indicating that localised heating may exceed 100 °C during prolonged industrial-scale manufacturing. Despite this, the influence of elevated temperature on tablet compaction remains insufficiently understood, particularly for commonly used excipients that lacking a measurable glass transition temperatures (Tg) and multi-component formulations. Furthermore, the impact of temperature on different tablet shapes and sizes remains underexplored.
This thesis investigates the impact of compacting tablets at elevated temperature (70 °C) through three studies: (1) assessing commonly used pure excipients, microcrystalline cellulose, starch, and lactose monohydrate; (2) evaluating multi-component placebo formulations exhibiting plastic, elastic, and brittle deformation characteristics; and (3) examining tablets of different sizes and shapes (flat and convex, 6 mm and 10 mm). Results reveal that temperature effects are highly dependent on excipient type, formulation composition, and the geometry of round tablets.
At 70 °C, microcrystalline cellulose exhibited increased plasticity and tabletability, starch demonstrated enhanced compressibility but reduced elastic recovery, and lactose displayed greater plastic deformation suggesting that the impact of temperature may extend beyond the proximity to the material’s Tg.
Multi-component formulations showed varying responses: the plastic formulation exhibited greater densification and tabletability; the brittle formulation showed only moderate increases; and the elastic formulation demonstrated the largest reduction in yield pressure.
Disintegration testing revealed that compaction at 70 °C significantly delayed disintegration for plastic (35 ± 3 seconds to 150 ± 13 seconds) and elastic (15 ± 3 seconds to 93 ± 15 seconds) formulations at a fixed compaction pressure, with similar trends observed when compacted to a solid fraction of 0.85. In contrast, the brittle formulation exhibited minimal change under both conditions. The delays observed suggest temperature-induced changes in particle bonding and microstructure. All formulations remained within USP disintegration limits, but temperature-sensitive formulations may be at risk of performance variability during manufacturing scale-up.
Tablet shape and size also influenced compaction outcomes at different temperatures. The plastic formulation showed consistent temperature-induced rises in compressibility across all the tested tablet shapes and sizes, while the elastic and brittle formulations responses varied. Hyperspectral imaging revealed non-uniform stress distribution across the tested tablet shapes and sizes, suggesting that an elevated die temperature may disrupt uniform stress distribution during double-sided compression.
These findings underscore the need for direct experimental evaluation of temperature effects in tabletting, to avoid undesired changes in tablet properties when scaling up from development to commercial manufacturing scale, rather than relying on often hard-to-measure thermal properties of excipients.
Supervisor
O'Mahony, Marcus A.
Soulimane, Tewfik
Soulimane, Tewfik
Description
Publisher
University of Limerick
Citation
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Funding Information
Sustainable Development Goals
External Link
Type
Thesis
Rights
http://creativecommons.org/licenses/by-nc-sa/4.0/