Pharmaceutical Research

, Volume 28, Issue 9, pp 2311–2326 | Cite as

Compositional Analysis of Low Quantities of Phase Separation in Hot-Melt-Extruded Solid Dispersions: A Combined Atomic Force Microscopy, Photothermal Fourier-Transform Infrared Microspectroscopy, and Localised Thermal Analysis Approach

  • Sheng Qi
  • Peter Belton
  • Kathrin Nollenberger
  • Andreas Gryczke
  • Duncan Q. M. Craig
Research Paper



To characterise phase separations in aged hot-melt-extruded solid dispersions at a micron to submicron scale.


Hot-melt-extruded felodipine and Eudragit® E PO systems at a range of compositions were studied after a standard period of aging to allow phase separation to occur. The samples were characterised using combined nano-thermal analysis, photothermal FTIR microspectroscopy coupled with pulsed force mode AFM as a novel characterisation approach.


Crystalline felodipine presents in all formulations with drug loadings from 10–70% (w/w). In formulations with high drug loadings (50 and 70%), amorphous felodipine co-exists with crystalline forms, and higher drug concentration is observed in the centre compared to the outer surface of the extrudates. Drug crystal dimensions in extrudates with low drug loadings (10–30%) are small, in the micron to submicron range. We propose that uneven drug distribution is principally caused by processing-associated factors such as expansion of extrudates during extrusion.


We have demonstrated that the novel combined approach allows site-specific characterisation of the extruded systems and that drug distribution may be uneven across the extrudates, with concomitant implications for understanding stability and drug release behaviour.


hot-melt-extruded solid dispersion phase separation photothermal FTIR microspectroscopy pulsed force mode atomic force microscopy supersaturation 



The authors would like to thank Dr. Jonathon Moffat and Prof. Mike Reading for their assistance on the use of PT-FTIR microspectroscopy.

Supplementary material

11095_2011_461_MOESM1_ESM.doc (4.6 mb)
Suppoting data (DOC 4760 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Sheng Qi
    • 1
  • Peter Belton
    • 2
  • Kathrin Nollenberger
    • 3
  • Andreas Gryczke
    • 3
  • Duncan Q. M. Craig
    • 1
  1. 1.School of PharmacyUniversity of East AngliaNorwichUK
  2. 2.School of ChemistryUniversity of East AngliaNorwichUK
  3. 3.Evonik Röhm GmbHDarmstadtGermany

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