Hot Stage Microscopy

Hot-stage Microscopy (HSM) is the combination of Microscopy and thermal analysis to enable the study of materials as a function of temperature and time. Besides obtaining information about particle size and particle morphology, the visual examination gives valuable information about the compound melting point and other transformations during heating. Hot Stage Microscopy gives a unique opportunity to follow thermal changes visually. 

With the aid of Hot Stage Microscopy, you can:

  1. Look at the compound morphology
  2. Study and visualise solid-solid transformations
  3. Monitor interactions between different compounds
  4. Observe dissolution of one compound in another
  5. Investigate sublimation and evaporation
  6. Follow melting or liquefaction upon heating (solid-liquid purity transformations)
  7. Explore solidification upon cooling (liquid-solid transformations)
  8. Watch crystal growth and rate thereof 
  9. Perform salt/co-crystal screening using Kofler mixed fusion method
  10. Observe oxidation and other chemical reactions upon heating

Further, characteristics that can be analysed under a hot stage microscope include melting range (which depends on the purity), crystal nucleation and crystal growth (which can be used in the search for new polymorphic forms), crystal transformations and interactions between the compound and excipients (examination of compatibility). I.e. various pharmaceutical applications exist.

Hot Stage Microscopy can be used for:

Hot stage microscopy is used in our polymorph screening: An initial heating of the compound is a valuable starting point. It will instantly reveal new crystalline forms are developing during the heating and cooling of the compound.

For Material Experts: 

Instrument and measuring principle  

The instrument set-up comprises a heating stage (hot stage) with a sample holder coupled with a suitable polarised-light microscope and a system that allows measurements of video/pictures and temperature.

InstrumentOlympus BX-50 Microscope connected to a Mettler Toledo Hot Stage.
USP/Ph. Eur.non-GMP
Sample amount< 1 mg
Temperature R.T. to 375 °C
ResultMicroscope pictures/movie showing the transitions during heating

Consult our Experts

Dr. Wenbo Wang
QC Chemist

Dr. Anna Shevchenko
Principal Scientist

Literature

Berry DJ, Seaton CC, Clegg W, Harrington RW, Coles SJ, Horton PN, Hursthouse MB, Storey R, Jones W, Friscic T, Blagden N (2008) Applying hot-stage microscopy to co-crystal screening: a study of nicotinamide with seven active pharmaceutical ingredients. Cryst Growth Des 8(5):1697-1712.

Koradia V, de Diego HL, Elema MR, Rantanen J (2010) Integrated approach to study the dehydration kinetics of nitrofurantoin monohydrate. Journal of pharmaceutical sciences. 99(9):3966-3976.

Lekšić E, Pavlović G, Meštrović E (2012) Co-crystals of lamotrigine based on conformers involving carbonyl group discovered by hot-stage Microscopy and DSC screening. Cryst Growth Des. 12(4):1847-1858.

Mura P, Faucci MT, Manderioli A, Bramanti G, Ceccarelli L (1998) Compatibility study between ibuproxam and pharmaceutical excipients using differential scanning calorimetry, hot-stage Microscopy and scanning electron microscopy. J Pharm Biomed 18(1-2):151-163.

Vitez IM, Newman AW, Davidovich M, Kiesnowski C (1998) The evolution of hot-stage Microscopy to aid solid-state characterisations of pharmaceutical solids. Thermochim Acta 324(1-2):187-196. 

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