TABLETING
DRY GRANULATION: MASTERING SMALL AMOUNTS
Exploring whether modelling is the future of early-stage oral solid dosage form development
Figure 1: Ultra small amount funnel, 50g Placebo trial, gap [mm] over time [s] H
andling small amounts is crucial in the development of oral solid dosage (OSD) forms. Efficiently defining
formulation and process parameters with minimal material reduces development costs, accelerates time to market, and enhances sustainability. Granulation, a pivotal step in OSD manufacturing, transforms powders into free-flowing, uniform granules. Dry granulation, in particular, is recognised for its simplicity, speed, and efficiency in OSD development.
LARGE SCALE EQUIPMENT Typically, dry-granulation equipment is designed and built for large scale to overcome flowability issues of the poorly flowing powder. Large scale equipment used to come with the downside of not being able to handle small amounts efficiently. High yields are hard to achieve owing to the large surface and potential loss area of the equipment. Furthermore,
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achieving a steady process as fast as possible is essential to avoid out-of- specification output. One approach to address early-stage
development challenges is the use of compaction simulators. These tools, combined with modern modelling techniques such as those based on the thin-layer model or Johanson’s work, facilitate the transfer of results to production-scale roller compactors. However, this method necessitates certain compromises. Correction factors must be determined to allow a scale-up from the compaction simulator to the roller compactor. These factors are essential for scaling up from the simulator to the roller compactor but require valuable material and introduce model uncertainty. An alternative approach involves
the use of small benchtop roller compactors. These compactors, characterised by smaller dimensions and reduced surface area, enable high yields when processing small amounts
of material. Despite their advantages, benchtop roller compactors face similar flowability issues as tableting equipment, and exhibit reduced draw- in capabilities due to their reduced dimensions. These limitations can lead to the erroneous conclusion that roller compaction is unsuitable for certain products, despite potential success with full-scale equipment.
FULL-SCALE ROLLER COMPACTORS Utilising full-scale roller compactors for small-scale development circumvents the need for modelling and mitigates the risk of false assumptions. By implementing several modifications to standard equipment, the process can be optimised to handle small quantities efficiently, achieving high yields and rapid steady-state conditions. In dry granulation, press force and gap are critical parameters influencing product characteristics. The flexible gap system maintains constant press
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