Hot Stage Microscopy (non-GMP)

Introduction

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 with regard to melting point and other transformations during heating. Hot Stage Microscopy gives an unique opportunity to visually follow thermal changes.

Further, characteristics that can be analyzed under a hot stage microscope include melting range (which depends on the purity), crystal nucleation and crystal growth (which can be used in 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:
  1. Compound morphology
  2. Solid-solid transformations
  3. Interaction between different compounds
  4. Dissolution of one compound in another
  5. Sublimation and/or evaporation
  6. Melting or liquefaction upon heating (solid-liquid transformations)
  7. Solidification upon cooling (liquid-solid transformations)
  8. Crystal growth and rate thereof

Hot stage microscopy is used in our polymorph screening: A initial heating of the compound is a very useful starting point, as it will instantly reveal new crystalline forms developing during heating and cooling of the compound.

Watch the beauty of a pharmaceutical crystal melting and recrystallising on a Hot Stage Microscope.

Instrument and measuring principle

The instrument setup comprises of a heating stage (hot stage) with a sample holder coupled with a suitable polarized-light microscope and a system that allows measurements of video/pictures and temperature. Click here to see an example of a crystal melting of a pharmaceutical compound- followed by recrystallisation of a new form at higher temperature. Note: Melting is seen as disapperance of the colorful particles from. Afterwards  new colors (crystals) is formed from the melt.

 

Technical info
Instrument Olympus BX-50 Microscope connected to a Mettler Toledo Hot Stage.
Sample amount < 1 mg
Temperature  RT to 375 °C
Result Microscope pictures/movie showing the transitions during heating
 
Photo from a Hot-Stage Microscope. A compound after melting and re-crystallisation. Transformations can be quite beautiful!