Flowing properties of spray-dried powders before and after granulation

Abstract

We study the flowing properties, the density and the packing dynamics of spray-dried powders produced with different nozzels and different airflow rates. At the exception of one powder, the obtained grains are small and have a low flowability due to cohesiveness. Therefore, an extrastreaming process is necessary before tableting. The spray-dried grains have been granulated with both High shear granulation (HSG) process and Fluid bed top spray granulation (FBG) process.

The obtained granules have a lower cohesiveness than the spray-dried powder. We show how the association of three recently developed flow measurement techniques (improved angle of repose measurement with GranuHeap instrument, cohesiveness measurement with GranuDrum instrument and improved tapped density measurement with GranuPack instrument) can be used to draw conclusion about the process-ability in a tableting process. Finally, we show how these results are correlated with grain sizes/shape distributions.

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Introduction

Granular materials, fine powders and nanostructured powders are widely used in pharmaceutical industrial applications [1-4]. Roughly 80% of the pharmaceutical products in US are tablets and capsules involving powders and granular materials [1]. A robust manufacturing process involving powder requires reliable powder flow properties. Unfortunately, pharmaceutical powders are usually cohesive and a deep understanding of the forces acting between the grains is necessary. Moreover, post-processing methods are commonly used to reduce the cohesiveness [5,6].

Powder behaviour is influenced by (i) steric repulsions, (ii) friction forces (iii) cohesive forces and (iv) interaction with the surrounding gas [7,8]. The steric repulsion is related to the grain geometry. Friction forces are influenced by both surface state (rough or smooth surface) and chemical nature of the grains. Cohesive forces may be induced by the presence of liquid bridges [9,10], by electrostatic charges [11-14], by van der Waals interactions [15] or more rarely by magnetic dipoledipole interactions[16]. The predominance of one of these forces depends on both the environmental conditions and the physico-chemical properties of the grains.

In the present paper, we show how spray-dried powders can be characterized before and after granulation with recently developed measurement devices to predict the process-ability (for example tableting). According to the spray-drying method, in particular according to the nozzle characteristics, the obtained powder is processable or not. Afterward, we discuss how the granulation step modifies powder flowing behaviour. In particular, we focus on two granulation methods: High shear granulation (HSG) process and Fluid bed top spray granulation (FBG) process.