(138b) Twin Screw Granulation: A Step Towards Continuous Processing

TWIN SCREW
GRANULATION: A STEP TOWARDS CONTINUOUS PROCESSING

Rachael Shinebaum^a,
Andrew Ingram^a, Hannah Batchelor^a,
Gavin K. Reynolds^b, Ian Gabbott^b

^a. School of Chemical Engineering,
University of Birmingham, Edgbaston, B15 2TT

^b. Pharmaceutical Technology & Development, Astra
Zeneca, Macclesfield, SK10 2NA

Within the pharmaceutical
industry, a shift towards continuous processing to produce granules, away from
traditional batch-wise techniques is underway. Twin Screw Granulation (TSG) is
a continuous process which, in recent years, has been the subject of much
research to increase knowledge in its role within solid oral dosage form
manufacturing. TSG reduces plant footprint, reduces process development costs
and allows ease of scale-up to full production. Within the TSG process there
are a large number of variable process parameters including: screw element
configuration, screw speed, liquid feed quantity and powder feed rate. Further
work is required to gain a deep understanding of the mechanisms and process
factors required to predict the characteristics and quality of the resulting
granules required by the FDA regulations, for example Quality by Design (QbD) and Process Analytical Technology (PAT).

This study investigates the
impacts of liquid to solid ratio and screw configuration on the properties of
the granules produced by the twin-screw granulator and their subsequent compaction
behaviour and tablet properties. A blend of lactose, microcrystalline cellulose
(MCC) and hydroxypropyl cellulose (HPC) was
granulated using six different liquid to solid ratios and five different screw
configurations. The granules were characterised with X-Ray micro tomography to
measure porosity and structure, while shape and size analysis was carried out
via QICPIC particle size analyser. Granule size increased dramatically with
increasing liquid content and kneading zones within the barrel. Tabletability was shown also to be affected by the granule
manufacturing conditions and was correlated with the granule.