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A Colourful Way to Unravel the Important Fluidization-Related Granule Size Effect on Semi-Continuous Drying

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Abstract

Continuous twin screw wet granulation (TSWG) systems are possible pathways for oral solid dosage manufacturing in the pharmaceutical industry. TSWG requires a drying step after granulation before the tableting process. Typically, semi-continuous fluidized bed dryers (FBDs) are used for this purpose. At the same time, the pharmaceutical sector is interested in mathematical prediction models to save resources during the early drug product development (DPD) stage or to control manufacturing. Several authors have already developed prediction models for semi-continuous drying processes. However, these model structures reported systematic prediction offsets, which could be related to the incomplete implementation of fluidization and granule segregation phenomena. This study evaluates the complex fluidization behavior of wet granules in industrially relevant semi-continuous FBDs. A transparent perspex version of the dryer was used for the analysis of bed height, pressure drop, porosity, segregation, and spatial heating patterns at varying process settings. The investigated behaviors of the fluidizing bed will be helpful to derive phenomenological (sub)models for the detailed description of segregation in the semi-continuous fluidized bed system. In this study, it was found that semi-continuous FBDs are characterized by a change in fluidization regime from plug flow to a bubbling bed at the moment that the granule bed slumps. Secondly, the presence of size-based vertical segregation phenomena as well as spatial temperature differences were proven. The experimental results suggest that larger granules are dried under more intense drying conditions than smaller granules.

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Abbreviations

Abbr.:

Description

API :

active pharmaceutical ingredient

C1 :

ConsiGma™-1

C25 :

ConsiGma™-25

CQA :

critical quality attribute

DPD :

drug product development

FBD :

fluidized bed dryer

GSD :

granule size distribution

LS :

liquid-to-solid

MFR :

mass flow rate

QbD :

quality by design

TSWG :

twin-screw wet granulation

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Funding

This work was supported by Ghent University.

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Authors and Affiliations

  1. Department of Data Analysis and Mathematical Modelling, BIOMATH, Ghent University, Oost-Vlaanderen, Belgium

    Tuur Vandeputte, Michael Ghijs & Ingmar Nopens

  2. Department of Pharmaceutical Analysis, Laboratory of Pharmaceutical Process Analytical Technology, Ghent University, Oost-Vlaanderen, Belgium

    Tuur Vandeputte, Michael Ghijs & Thomas De Beer

Authors
  1. Tuur Vandeputte
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  2. Michael Ghijs
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  4. Thomas De Beer
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Contributions

T. Vandeputte: Conceptualization, Methodology, Software, Investigation, Validation, Visualization, Writing - original draft M. Ghijs: Conceptualization, Methodology, Software, Investigation, Validation, Writing - review & editing I. Nopens: Conceptualization, Methodology, Software, Writing - review & editing, Project administration T. De Beer: Conceptualization, Methodology, Investigation, Validation,Writing - review & editing, Project administration. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Tuur Vandeputte.

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Vandeputte, T., Ghijs, M., Nopens, I. et al. A Colourful Way to Unravel the Important Fluidization-Related Granule Size Effect on Semi-Continuous Drying. AAPS PharmSciTech 25, 11 (2024). https://doi.org/10.1208/s12249-023-02711-8

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