---
_id: '12781'
abstract:
- lang: eng
  text: Roller compaction/dry granulation (RC/DG) is a key process in pharmaceutical
    manufacturing for improving powder flowability, density, and segregation resistance.
    Advanced statistical modeling was used to optimize RC/DG process parameters and
    subsequently binder compositions by employing process and mixture design experiments.
    The authors used microcrystalline cellulose (MCC), silicified MCC (SMCC), and
    dicalcium phosphate (DCP) as filler-binder examples in RC/DG experiments. Granule
    and tablet properties, including flowability, bulk and tapped densities, as well
    as resistance to crushing, were analyzed using compendial methods. The process
    design experiments confirmed that RC/DG reduces manufacturability compared to
    direct compression. Optimal processing conditions, balancing sufficient tablet
    strengths and granule formation, were identified to be between 20 (SCF * ϑ) [kN/cm]
    and ∼ 60 (SCF * ϑ) [kN/cm]. Thereby (ϑ) is defined as the screw-to-roll speed
    ratio and (SFC) as the specific compaction force. Mixture design experiments revealed
    optimal mixtures balancing SMCC, MCC, and DCP to achieve desired properties like
    low angle of repose, high bulk density, and strong tablets. These findings provide
    guidance for selecting formulations and process parameters in RC/DG applications.
    The derived ‘SCF * ϑ’- factor was found to effectively describe the granulation
    intensity. A superimposed mixture design model based on precise target values
    of the parameters bulk density, flow properties, and breaking force allowed identification
    of the best formulation.
article_number: '100331'
author:
- first_name: Niclas
  full_name: Märkle, Niclas
  id: '74898'
  last_name: Märkle
- first_name: Gernot
  full_name: Warnke, Gernot
  last_name: Warnke
- first_name: Miriam
  full_name: Pein-Hackelbusch, Miriam
  id: '64952'
  last_name: Pein-Hackelbusch
  orcid: 0000-0002-7920-0595
citation:
  ama: 'Märkle N, Warnke G, Pein-Hackelbusch M. An iterative process and mixture design
    approach for dry granulated ternary blends of filler-binders. <i>International
    Journal of Pharmaceutics: X</i>. 2025;9. doi:<a href="https://doi.org/10.1016/j.ijpx.2025.100331">10.1016/j.ijpx.2025.100331</a>'
  apa: 'Märkle, N., Warnke, G., &#38; Pein-Hackelbusch, M. (2025). An iterative process
    and mixture design approach for dry granulated ternary blends of filler-binders.
    <i>International Journal of Pharmaceutics: X</i>, <i>9</i>, Article 100331. <a
    href="https://doi.org/10.1016/j.ijpx.2025.100331">https://doi.org/10.1016/j.ijpx.2025.100331</a>'
  bjps: '<b>Märkle N, Warnke G and Pein-Hackelbusch M</b> (2025) An Iterative Process
    and Mixture Design Approach for Dry Granulated Ternary Blends of Filler-Binders.
    <i>International Journal of Pharmaceutics: X</i> <b>9</b>.'
  chicago: 'Märkle, Niclas, Gernot Warnke, and Miriam Pein-Hackelbusch. “An Iterative
    Process and Mixture Design Approach for Dry Granulated Ternary Blends of Filler-Binders.”
    <i>International Journal of Pharmaceutics: X</i> 9 (2025). <a href="https://doi.org/10.1016/j.ijpx.2025.100331">https://doi.org/10.1016/j.ijpx.2025.100331</a>.'
  chicago-de: 'Märkle, Niclas, Gernot Warnke und Miriam Pein-Hackelbusch. 2025. An
    iterative process and mixture design approach for dry granulated ternary blends
    of filler-binders. <i>International Journal of Pharmaceutics: X</i> 9. doi:<a
    href="https://doi.org/10.1016/j.ijpx.2025.100331">10.1016/j.ijpx.2025.100331</a>,
    .'
  din1505-2-1: '<span style="font-variant:small-caps;">Märkle, Niclas</span> ; <span
    style="font-variant:small-caps;">Warnke, Gernot</span> ; <span style="font-variant:small-caps;">Pein-Hackelbusch,
    Miriam</span>: An iterative process and mixture design approach for dry granulated
    ternary blends of filler-binders. In: <i>International Journal of Pharmaceutics:
    X</i> Bd. 9. Amsterdam, Elsevier BV (2025)'
  havard: 'N. Märkle, G. Warnke, M. Pein-Hackelbusch, An iterative process and mixture
    design approach for dry granulated ternary blends of filler-binders, International
    Journal of Pharmaceutics: X. 9 (2025).'
  ieee: 'N. Märkle, G. Warnke, and M. Pein-Hackelbusch, “An iterative process and
    mixture design approach for dry granulated ternary blends of filler-binders,”
    <i>International Journal of Pharmaceutics: X</i>, vol. 9, Art. no. 100331, 2025,
    doi: <a href="https://doi.org/10.1016/j.ijpx.2025.100331">10.1016/j.ijpx.2025.100331</a>.'
  mla: 'Märkle, Niclas, et al. “An Iterative Process and Mixture Design Approach for
    Dry Granulated Ternary Blends of Filler-Binders.” <i>International Journal of
    Pharmaceutics: X</i>, vol. 9, 100331, 2025, <a href="https://doi.org/10.1016/j.ijpx.2025.100331">https://doi.org/10.1016/j.ijpx.2025.100331</a>.'
  short: 'N. Märkle, G. Warnke, M. Pein-Hackelbusch, International Journal of Pharmaceutics:
    X 9 (2025).'
  ufg: '<b>Märkle, Niclas/Warnke, Gernot/Pein-Hackelbusch, Miriam</b>: An iterative
    process and mixture design approach for dry granulated ternary blends of filler-binders,
    in: <i>International Journal of Pharmaceutics: X</i> 9 (2025).'
  van: 'Märkle N, Warnke G, Pein-Hackelbusch M. An iterative process and mixture design
    approach for dry granulated ternary blends of filler-binders. International Journal
    of Pharmaceutics: X. 2025;9.'
date_created: 2025-04-11T08:39:07Z
date_updated: 2025-05-08T08:20:23Z
department:
- _id: DEP4022
- _id: DEP4028
doi: 10.1016/j.ijpx.2025.100331
external_id:
  pmid:
  - '40242454 '
intvolume: '         9'
keyword:
- Design of experiments
- Roller compaction/dry granulation
- RC/DG
- Dicalcium phosphate
- Microcrystalline cellulose
- Silicified microcrystalline cellulose
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.sciencedirect.com/science/article/pii/S2590156725000167
oa: '1'
place: Amsterdam
pmid: '1'
publication: 'International Journal of Pharmaceutics: X'
publication_identifier:
  eissn:
  - 2590-1567
  issn:
  - 1873-3476
publication_status: published
publisher: Elsevier BV
quality_controlled: '1'
status: public
title: An iterative process and mixture design approach for dry granulated ternary
  blends of filler-binders
type: scientific_journal_article
user_id: '83781'
volume: 9
year: '2025'
...