Pharmaceutical Research

, Volume 24, Issue 11, pp 2048–2054 | Cite as

Nanoscale Characterisation and Imaging of Partially Amorphous Materials using Local Thermomechanical Analysis and Heated Tip AFM

Research Paper

Abstract

Purpose

The purpose is to investigate the use of thermal nanoprobes in thermomechanical and heated tip pulsed force modes as novel means of discriminating between amorphous and crystalline material on a sub-micron scale.

Materials and methods

Indometacin powder was compressed and partially converted into amorphous material. Thermal nanoprobes were used to perform localised thermomechanical analysis (L-TMA) and heated tip pulsed force mode imaging as a function of temperature.

Results

L-TMA with submicron lateral spatial resolution and sub-100 nm depth penetration was achieved, allowing us to thermomechanically discriminate between amorphous and crystalline material at a nanoscale for the first time. The amorphous and crystalline regions were imaged as a function of temperature using heated tip pulsed force AFM and a resolution of circa 50 nm was achieved. We are also able to observe tip-induced recrystallisation of the amorphous material.

Discussion

The study demonstrates that we are able to discriminate and characterise amorphous and crystalline regions at a submicron scale of scrutiny. We have demonstrated the utility of two methods, L-TMA and heated tip pulsed force mode AFM, that allow us to respectively characterise and image adjacent amorphous and crystalline regions at a nanoscale.

Conclusions

The study has demonstrated that thermal nanoprobes represent a novel method of characterising and imaging partially amorphous materials.

Key words

amorphous atomic force microscopy glass transition indometacin microthermal analysis 

Abbreviations

AFM

atomic force microscopy

L-TMA

localised thermomechanical analysis

MTA

microthermal analysis

PFM

pulsed force mode

References

  1. 1.
    A. Hammiche, M. Reading, H. M. Pollock, M. Song, and D. J. Hourston. Localized thermal analysis using a miniaturized resistive probe. Rev. Sci. Instrum. 67:4268–4274 (1996).CrossRefGoogle Scholar
  2. 2.
    A. Hammiche, H. M. Pollock, M. Reading, M. Claybourn, P. H. Turner, and K. Jewkes. Photothermal FT-IR spectroscopy: a step towards FT-IR microscopy at a resolution better than the diffraction limit. Appl. Spectrosc. 53:810-815 (1999).CrossRefGoogle Scholar
  3. 3.
    H. M. Pollock and A. Hammiche. Micro-thermal analysis: techniques and applications. J. Phys. D: Appl. Phys. 34:R23–R53 (2001).CrossRefGoogle Scholar
  4. 4.
    L. Harding, J. Wood, M. Reading, and D. Q. M. Craig. Two- and three-dimensional imaging of multicomponent systems using scanning thermal microscopy and localized thermomechanical analysis. Anal. Chem. 79:129–139 (2007).PubMedCrossRefGoogle Scholar
  5. 5.
    G. H. W. Sanders, C. J. Roberts, A. Danesh, A. J. Murray, D. M. Price, M. C. Davies, S. J. B. Tendler, and M. J. Wilkins. Discrimination of polymorphic forms of a drug product by localized thermal analysis. J. Microsc. 198:77–81 (2000).PubMedCrossRefGoogle Scholar
  6. 6.
    A. Hammiche, L. Bozec, M. Conroy, H. M. Pollock, G. Mills, J. M. R. Weaver, D. M. Price, M. Reading, D. J. Hourston, and M. Song. Highly localized thermal, mechanical, and spectroscopic characterization of polymers using miniaturized thermal probes. J. Vac Sci. Technol. B 18:1322–1332 (2000).CrossRefGoogle Scholar
  7. 7.
    L. Harding, M. Reading, and D. Q. M. Craig. The development of heated tip force-distance measurements as a novel approach to site-specific characterisation of pharmaceutical materials. J Pharm Sci (accepted for publication) (2007).Google Scholar
  8. 8.
    B. A. Nelson and W. P. King. Measuring material softening with nanoscale spatial resolution using heated silicon probes. Rev. Sci. Instrum. 78:023702 (1–8) (2007).CrossRefGoogle Scholar
  9. 9.
    W. P. King, S. Saxena, B. A. Nelson, B. L. Weeks, and R. Pitchimani. Nanoscale thermal analysis of an energetic material. Nano. Lett. 6:2145–2149 (2006).PubMedCrossRefGoogle Scholar
  10. 10.
    T. Gray, J. Killgore, J. Luo, A. K. Y. Jen, and R. M. Overney. Molecular mobility and transitions in complex organic systems studied by shear force microscopy. Nanotechnology 18:1–9 (2007).CrossRefGoogle Scholar
  11. 11.
    P. G. Royall, V. L. Kett, C. S. Andrews, and D. Q. M. Craig. Identification of crystalline and amorphous regions in low molecular weight materials using microthermal analysis. J. Phys. Chem. B 105:7021–7026 (2001).CrossRefGoogle Scholar
  12. 12.
    C. Ahlneck and G. Zografi. The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state. Int. J. Pharm. 62:87–95 (1990).CrossRefGoogle Scholar
  13. 13.
    K. R. Morris, U. J. Griesser, C. J. Eckhardt, and J. G. Stowell. Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes. Adv. Drug Deliv. Rev. 48:91–114 (2001).PubMedCrossRefGoogle Scholar
  14. 14.
    L. Yu. Amorphous pharmaceutical solids: preparation, characterization and stabilization. Adv. Drug Deliv. Rev. 48:27–42 (2001).PubMedCrossRefGoogle Scholar
  15. 15.
    S. Ward, M. Perkins, J. Zhang, C. J. Roberts, C. E. Madden, S. Y. Luk, N. Patel, and S. J. Ebbens. Identifying and mapping surface amorphous domains. Pharm. Res. 22:1195–1202 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    M. Reading, D. M. Price, D. B. Grandy, R. M. Smith, L. Bozec, M. Conroy, A. Hammiche, and H. M. Pollock. Micro-thermal analysis of polymers: current capabilities and future prospects. Macromol. Symp. 167:45–62 (2001).CrossRefGoogle Scholar
  17. 17.
    D. Mahlin, J. Berggren, G. Alderborn, and S. Engström. Moisture-induced surface crystallization of spray-dried amorphous lactose particles studied by atomic force microscopy. J. Pharm. Sci. 93:29–37 (2004).PubMedCrossRefGoogle Scholar
  18. 18.
    R. Price and P. M. Young. Visualization of the crystallization of lactose from the amorphous state. J. Pharm. Sci. 93:155–164 (2004).PubMedCrossRefGoogle Scholar
  19. 19.
    P. Begat, P. M. Young, S. Edge, J. S. Kaerger, and R. Price. The effect of mechanical processing on surface stability of pharmaceutical powders: visualization by atomic force microscopy. J. Pharm. Sci. 92:611–620 (2003).PubMedCrossRefGoogle Scholar
  20. 20.
    D. B. Grandy, D. J. Hourston, D. M. Price, M. Reading, G. G. Silva, M. Song, and P. A. Sykes. Microthermal characterization of segmented polyurethane elastomers and a polystyrene—poly(methyl methacrylate) polymer blend using variable-temperature pulsed force mode atomic force microscopy. Macromolecules 33:9348–9359 (2000).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.School of Chemical Sciences and PharmacyUniversity of East AngliaNorwichUK
  2. 2.Department of Mechanical Science and EngineeringUniversity of Illinois Urbana-ChampaignUrbanaUSA

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