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Experimental and modelistic approach to explain granulate inhomogeneity through preferential growth
Kaspar van den Dries1, Herman Vromans
1Department of Pharmaceutics, N.V. Organon, AKZO-NOBEL, Room RK2216, P.O. Box 20, 5340 BH Oss, The Netherlands. kaspar.vandendries@organon.com
Summary
Small particles preferentially accumulate in granules during wet granulation, leading to inhomogeneous mixtures. This study investigated preferential growth mechanisms, finding fine particles have a higher affinity for granule growth.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Wet granulation commonly produces inhomogeneous granules due to preferential particle uptake.
- The accumulation of fine particles in larger granules is a known issue.
Purpose of the Study:
- To investigate the mechanism behind preferential particle growth during wet granulation.
- To understand why fine particles are preferentially incorporated into granules.
Main Methods:
- Studied the growth of single granules by adding binder liquid to rotating paracetamol and lactose mixtures.
- Varied particle sizes of both components and analyzed granule mass and paracetamol content over time.
Main Results:
- Fine particles consistently showed higher relative presence in granules compared to coarse particles.
- This preferential uptake was observed regardless of whether fine particles were paracetamol or lactose.
- Fine particles demonstrated a higher affinity for granule growth during liquid-induced layering.
Conclusions:
- Fine particles are preferentially absorbed due to easier penetration into granule pores.
- A model based on this mechanism successfully predicted experimental outcomes.
- This non-random growth process is the underlying cause of inhomogeneous granule formation.