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Image Analysis Quantification of Sticking and Picking Events of Pharmaceutical Powders Compressed on a Rotary Tablet Press Simulator

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ABSTRACT

Purpose

The aim of this work was to develop a quantification method based on image analysis, able to characterize sticking during pharmaceutical tableting. Relationship between image analysis features and relevant mechanical parameters recorded on an instrumented tablet press simulator were investigated.

Methods

Image analysis, based on gray levels co-occurrence matrices (GLCM), generated textural features of the tablet surface. The tableting simulator (Stylcam® 200R, Medelpharm), instrumented with force and displacement transducers, provided accurate records. The tablet defects and compaction process parameters were studied using three pharmaceutical powders (Fast-Flo® lactose, anhydrous Emcompress® and Avicel® PH200 microcrystalline cellulose), five compression pressures (60 to 250 MPa), five lubricating levels, and three types of punches (standard steel, amorphous hard carbon and anti-sticking punches).

Results

Texture parameters made it possible to quantify with precision tablets’ aspect. The selected parameter IC2 (Information on Correlation 2) plotted versus the ratio between the ejection shear stress (Esh) and the compression pressure (Cp) let appear a relevant knowledge space where it was possible to identify a normal and a degraded tableting mode. A positive link between those two parameters was shown.

Conclusion

Since the Esh/Cp ratio was related to image analysis results, it proved to be an interesting defect tag.

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Notes

  1. Some series have not been represented because their attached result did not make sense. For instance, low pressures series of Emcompress® had high values of IC2, not because the tablets were degraded, but because the individual particles of powder were still visible due to the low pressure, mimicking a kind of roughness, not linked to a defect (27). Indeed, Emcompress® had big, and brittle particles. This phenomenon appeared for some Avicel® series too (see Table I).

Abbreviations

AHC:

amorphous hard carbon

API:

active pharmaceutical ingredient

AS:

anti sticking

Cp:

compression pressure

Ent:

entropy parameter

Esh:

ejection shear stress

GLCM:

gray level co-occurrence matrix

IC2:

information on correlation 2

StdStl:

standard steel

WTA:

wavelet texture analysis

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors gratefully acknowledge Louis Henrion and Yves Collenot from Sanofi for image analysis and photography assistance, Cécile Gagaude from Sanofi for reviewing.

The authors would like to thank EPMO and SFOB for supplying free punches, Noesis for efficient support and updating of the image analysis software Visilog 6.8, Medelpharm for tableting assistance and Sanofi where experiments have been carried out, for their financial support.

The authors wish to thank Mrs Stella Ghouti Baxter for proof reading and grammar correction of the document.

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Authors and Affiliations

  1. Univ Paris-Sud, UFR de Pharmacie, EA 401, Matériaux et Santé 5 rue Jean-Baptiste Clément, Châtenay-Malabry, 92296, France

    Germinal Mollereau, Vincent Mazel, Virginie Busignies & Pierre Tchoreloff

  2. Sanofi, Product and Process Development, Pharmaceutical Sciences Department, 13 Quai Jules Guesde, BP 14, 94403, Vitry-sur-Seine Cedex, France

    Fabrice Mouveaux & Philippe Rivière

Authors
  1. Germinal Mollereau
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  2. Vincent Mazel
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  3. Virginie Busignies
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  4. Pierre Tchoreloff
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  5. Fabrice Mouveaux
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  6. Philippe Rivière
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Corresponding author

Correspondence to Pierre Tchoreloff.

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Mollereau, G., Mazel, V., Busignies, V. et al. Image Analysis Quantification of Sticking and Picking Events of Pharmaceutical Powders Compressed on a Rotary Tablet Press Simulator. Pharm Res 30, 2303–2314 (2013). https://doi.org/10.1007/s11095-013-1074-8

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  • DOI: https://doi.org/10.1007/s11095-013-1074-8

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