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Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying

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Abstract

Purpose

It was investigated if continuous wet granulation and drying could be combined in a twin-screw granulator with the aim to provide (pre-)dried granules in a single-step process, i.e. in-barrel-drying.

Methods

To have a consistent and robust material propulsion mechanism, a twin-screw granulator was divided into two compartments. One compartment was operated at lower temperature to granulate and to pre-heat the material, while another compartment was operated at very high temperature to evaporate the granulation liquid as rapidly as possible. Design of experiments was used to investigate the in-barrel-drying process in detail. The process was further investigated for twin-screw wet granulation with API suspension feed, and compared against traditional fluidised-bed drying. Granule and compact properties were evaluated to study the process impact on the product quality.

Results

In-barrel-drying was demonstrated as feasible and yielded completely dried and granulated material at specific settings. The evaporation zone temperature and the processed mass of water were identified as key parameters to balance the evaporation capacity of the process and the material throughput. Granules and compacts showed an acceptable product quality.

Conclusions

In-barrel-drying can be used to condense the wet granulation and drying process steps into one piece of equipment, thereby limiting or even omitting downstream drying process steps.

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Abbreviations

API:

Active pharmaceutical ingredient

CP:

Centre point

DOE:

Design of experiments

HPLC:

High performance liquid chromatography

L/S ratio:

Liquid-to-solid mass flow ratio

LOD:

Loss-on-drying

ScSp:

Screw speed

Temp.Eva:

Temperature in the evaporation zone

Temp.Pre:

Temperature in the pre-heating zone

TMMF:

Total material mass flow rate

TSG:

Twin-screw granulator

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Authors and Affiliations

  1. Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, 40225, Duesseldorf, Germany

    Adrian Schmidt & Peter Kleinebudde

  2. Novartis AG, WSJ-027.4.015, Novartis Campus, 4002, Basel, Switzerland

    Adrian Schmidt, Hans de Waard & Markus Krumme

Authors
  1. Adrian Schmidt
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  2. Hans de Waard
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  3. Peter Kleinebudde
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  4. Markus Krumme
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Corresponding author

Correspondence to Markus Krumme.

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Schmidt, A., de Waard, H., Kleinebudde, P. et al. Continuous Single-Step Wet Granulation with Integrated in-Barrel-Drying. Pharm Res 35, 167 (2018). https://doi.org/10.1007/s11095-018-2451-0

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  • DOI: https://doi.org/10.1007/s11095-018-2451-0

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