Pharmaceutical Research

, Volume 32, Issue 4, pp 1407–1416 | Cite as

Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions

  • Joke Meeus
  • David J. Scurr
  • Xinyong Chen
  • Katie Amssoms
  • Martyn C. Davies
  • Clive J. Roberts
  • Guy Van den MooterEmail author
Research Paper



Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix.


MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed.


MDSC, TOF-SIMS and AFM provided insights into differences in drug distribution via the observed surface coverage for 3 differently composed ternary solid dispersions.


Combining MDSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.


AFM MDSC Miscibility Solid dispersions ToF-SIMS 



Modulated differential scanning calorimetry


Atomic force microscopy


Active pharmaceutical ingredient


Drug delivery system


Human immunodeficiency virus


Poly(lactic-co-glycolic acid)




Glass transition temperature


Time of flight secondary ion mass spectrometry



Dr. Matthew Piggott (ISAC, Nottingham, United Kingdom) is acknowledged for coordinating the AFM experiments.

Supplementary material

11095_2014_1543_Fig10_ESM.gif (63 kb)
Figure 1

Negative ToF-SIMS spectra showing the markers for API (m/z = 183, C8H7SO3 ), PLGA (m/z = 143, C6H7O4 ) and PVP (m/z = 84, C5H8O). (GIF 62 kb)

11095_2014_1543_MOESM1_ESM.tif (138 kb)
High resolution image (TIFF 138 kb)
11095_2014_1543_Fig11_ESM.gif (16 kb)
Figure 2

Negative polarity ToF-SIMS spectra at m/z 84 (ion characteristic of PVP) of A. PVP and the model formulations with following API/PLGA/PVP (w/w/w) ratios. B. 10/75/15, C. 20/50/30, D. 30/25/45. (GIF 16 kb)

11095_2014_1543_MOESM2_ESM.tif (37 kb)
High resolution image (TIFF 36 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Joke Meeus
    • 1
  • David J. Scurr
    • 2
  • Xinyong Chen
    • 2
  • Katie Amssoms
    • 3
  • Martyn C. Davies
    • 2
  • Clive J. Roberts
    • 2
  • Guy Van den Mooter
    • 1
    Email author
  1. 1.Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological SciencesLeuvenBelgium
  2. 2.Laboratory of Biophysics and Surface Analysis, School of PharmacyThe University of NottinghamNottinghamUK
  3. 3.Pharmaceutical Companies of Johnson & Johnson, Janssen, Discovery Sciences, PD&S_PDMBeerseBelgium

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