AAPS PharmSciTech

, Volume 11, Issue 3, pp 1202–1205 | Cite as

Parallel Thermal Analysis Technology Using an Infrared Camera for High-Throughput Evaluation of Active Pharmaceutical Ingredients: A Case Study of Melting Point Determination

  • Kohsaku Kawakami
Brief/Technical Note


Various techniques for physical characterization of active pharmaceutical ingredients, including X-ray powder diffraction, birefringence observation, Raman spectroscopy, and high-performance liquid chromatography, can be conducted using 96-well plates. The only exception among the important characterization items is the thermal analysis, which can be a limiting step in many cases, notably when screening the crystal/salt form. In this study, infrared thermal camera technology was applied for thermal characterization of pharmaceutical compounds. The melting temperature of model compounds was determined typically within 5 min, and the obtained melting temperature values agreed well with those from differential scanning calorimetry measurements. Since many compounds can be investigated simultaneously in this infrared technology, it should be promising for high-throughput thermal analysis in the pharmaceutical developmental process.

Key words

high-throughput analysis infrared camera thermal analysis 



The author would like to thank Apiste (Osaka, Japan) for the use of the infrared camera. This work was in part supported by World Premier International Research Center (WPI) Initiative on Materials Nanoarchitectonics, MEXT, Japan.


  1. 1.
    Hilfiker R, Blatter F, von Raumer M. Relevance of solid-state properties for pharmaceutical products. In: Hilfiker R, editor. Polymorphism. Weinhelm: Wiley-VCH; 2006. p. 1–19.CrossRefGoogle Scholar
  2. 2.
    Pudipeddi M, Serajuddin ATM. Trends in solubility of polymorphs. J Pharm Sci. 2005;94:929–39.CrossRefPubMedGoogle Scholar
  3. 3.
    Miller JM, Collman BM, Greene LR, Grant DJW, Blackburn AC. Identifying the stable polymorph early in the drug discovery-development process. Pharm Dev Technol. 2005;10:291–7.PubMedGoogle Scholar
  4. 4.
    Kawakami K. Reversibility of enantiotropically related polymorphic transformations from a practical viewpoint: thermal analysis of kinetically reversible/irreversible polymorphic transformations. J Pharm Sci. 2007;96:982–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Bauer J, Spanton S, Henry R, Quick J, Dziki W, Porter W, et al. Ritonavir: an extraordinary example of conformational polymorphism. Pharm Res. 2001;18:859–66.CrossRefPubMedGoogle Scholar
  6. 6.
    Newman AW, Childs SL, Cowans BA. Salt and cocrystal form selection. In Preclinical development handbook. Hoboken: Wiley; 2008. Chapter 14.Google Scholar
  7. 7.
    Hilfiker R, De Paul SM, Szelagiewicz M. Approaches to polymorphism screening. In: Hilfiker R, editor. Polymorphism. Weinhelm: Wiley-VCH; 2006. p. 287–308.CrossRefGoogle Scholar
  8. 8.
    Henck JO, Byrn S. Designing a molecular delivery system within a preclinical timeframe. Drug Discovery Today. 2007;12:189–99.CrossRefPubMedGoogle Scholar
  9. 9.
    Kawakami K. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases. J Pharm Sci. 2009;98:2875–85.CrossRefPubMedGoogle Scholar
  10. 10.
    Telenkov SA, Vergas G, Nelson JS, Milner TE. Coherent thermal wave imaging of subsurface chromophores in biological materials. Phys Med Biol. 2002;47:657–71.CrossRefGoogle Scholar
  11. 11.
    Hashimoto T, Morikawa J. Two-dimensional microscale thermal analysis of freezing of onionskin cells by high-speed infrared focal plane arrays. J Appl Phys. 2003;42:L706–8.CrossRefGoogle Scholar
  12. 12.
    Meola C, Carlomagno GM. Application of infrared thermography to adhesion science. J Adhesion Sci Technol. 2006;20:589–632.CrossRefGoogle Scholar
  13. 13.
    Ng EYK. A review of thermography as promising non-invasive detection modality for breast cancer. Int J Therm Sci. 2009;48:849–59.CrossRefGoogle Scholar
  14. 14.
    Tan JH, Ng EYK, Rajendra Acharya U. Infrared thermography on ocular surface temperature: a review. Infrared Phys Technol. 2009;52:97–108.CrossRefGoogle Scholar
  15. 15.
    Kawakami K, Ida Y. Application of modulated-temperature DSC to the analysis of enantiotropically-related polymorphic transitions. Thermochim Acta. 2005;427:93–9.CrossRefGoogle Scholar
  16. 16.
    Crowley KJ, Zografi G. Cryogenic grinding of indomethacin polymorphs and solvates: assessment of amorphous phase formulation and amorphous phase physical stability. J Pharm Sci. 2002;91:492–507.CrossRefPubMedGoogle Scholar
  17. 17.
    Kett VL, Fitzpatrick S, Cooper B, Craig DQM. An investigation into the subambient behavior of aqueous mannitol solutions using differential scanning calorimetry, cold stage microscopy, and x-ray diffractometry. J Pharm Sci. 2003;92:1919–29.CrossRefPubMedGoogle Scholar
  18. 18.
    Xie Y, Cao W, Krishnan S, Lin H, Cauchon N. Characterization of mannitol polymorphic forms in lyophilized protein formulations using a multivariate curve resolution (MCR)-based Raman spectroscopic method. Pharm Res. 2008;25:2292–301.CrossRefPubMedGoogle Scholar
  19. 19.
    Kobayashi Y, Ito S, Itai S, Yamamoto K. Physicochemical properties and bioavailability of carbamazepine polymorphs and dehydrate. Int J Pharm. 2000;193:137–46.CrossRefPubMedGoogle Scholar
  20. 20.
    Grzesiak AL, Lang M, Kim K, Matzger AJ. Comparison of the four anhydrous polymorphs of carbamazepine and the crystal structure of form I. J Pharm Sci. 2003;92:2260–71.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang GGZ, Gu C, Zell MT, Burkhardt RT, Munson EJ, Grant DJW. Crystallization and transitions of sulfamerazine polymorphs. J Pharm Sci. 2002;91:1089–100.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  1. 1.National Institute for Materials ScienceBiomaterials CenterIbarakiJapan
  2. 2.International Center for Materials NanoarchitectonicsIbarakiJapan

Personalised recommendations