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

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Abstract

Purpose

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.

Methods

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.

Results

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

Conclusions

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

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Abbreviations

MDSC:

Modulated differential scanning calorimetry

AFM:

Atomic force microscopy

API:

Active pharmaceutical ingredient

DDS:

Drug delivery system

HIV:

Human immunodeficiency virus

PLGA:

Poly(lactic-co-glycolic acid)

PVP:

Polyvinylpyrrolidone

T g :

Glass transition temperature

ToF-SIMS:

Time of flight secondary ion mass spectrometry

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ACKNOWLEDGMENTS AND DISCLOSURES

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

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Authors and Affiliations

  1. Drug Delivery and Disposition, KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Campus Gasthuisberg ON2, Herestraat 49 b921, 3000, Leuven, Belgium

    Joke Meeus & Guy Van den Mooter

  2. Laboratory of Biophysics and Surface Analysis, School of Pharmacy, The University of Nottingham, Nottingham, UK

    David J. Scurr, Xinyong Chen, Martyn C. Davies & Clive J. Roberts

  3. Pharmaceutical Companies of Johnson & Johnson, Janssen, Discovery Sciences, PD&S_PDM, Beerse, Belgium

    Katie Amssoms

Authors
  1. Joke Meeus
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  2. David J. Scurr
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  3. Xinyong Chen
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  4. Katie Amssoms
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  5. Martyn C. Davies
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  6. Clive J. Roberts
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  7. Guy Van den Mooter
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Corresponding author

Correspondence to Guy Van den Mooter.

Electronic supplementary material

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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)

High resolution image (TIFF 138 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)

High resolution image (TIFF 36 kb)

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Meeus, J., Scurr, D.J., Chen, X. et al. Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions. Pharm Res 32, 1407–1416 (2015). https://doi.org/10.1007/s11095-014-1543-8

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  • DOI: https://doi.org/10.1007/s11095-014-1543-8

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