Hot Stage Microscopy For Pharma Application

  • Combines thermal analysis and microscopy to characterize solid-state materials over time and at different temperatures.
  • In pharmaceuticals HSM is used to support differential scanning calorimetry (DSC) and thermo-gravimetric analysis (TGA) observations and to detect small changes in the sample that may be missed by DSC and TGA during a thermal experiment.
  • HSM is used to observe crystallization process, desolation, polymorphism, phase transitions, melting/boiling points, glass transitions, etc of samples.


  • Morphology Study
  • Amorphous/Crystalline form characterization
  • Polymorphism
  • Cocrystal screening
  • Particle size distribution and characterization of an API in a Tablet
  • Solvates/Hydrates screening
  • Miscibility

Advanced Hot Stage Microscope Setup

    1. Software controlled hot stage with Temperature ramping facility. Allowing controlled heating and cooling as per rate defined.
    2. An optical Microscope with reflected and Transmitted light observation and allowing Bright field ,Dark field and polarized observation method.
    3. Image capturing facility with high frame Rate to capture image and video with temperature , date , time and micron marker stamping.
    4. The sample is heated on a glass slide with cover slip or without cover slip with compatible liquid so that heating is homogenous.
    5. Hot stage should allow controlled cooling and gas purge in chamber to allow experiment in various environmental condition.
    6. Hexon Hot stage have various Models to give temperature range from (-40 to 600 Deg C)

Morphology Study

    1. Solid- state property or morphology study of API particle
    2. Study Api changing shape while heating and regenerating as amorphous or crystalline while cooling.
    3. Melting point of API and excipients
    4. Real time visual observation helps understand small changes in surface which may be missed by DSC and TGA.

Amorphous/crystalline form characterization

    1. The amorphous form of API is preferred in the pharmaceutical industry due to their higher solubility and dissolution rates over crystalline forms
    2. With a hot stage microscope fitted with a polarizing filter, amorphous and crystalline forms are easily distinguishable from one another.
    3. Crystalline materials are known to show birefringence, while amorphous material lack birefringence , hence can easily be distinguished from crystalline compounds.
    4. HSM is a great tool to study the conversion of an amorphous API to crystalline form under the effect of heating
    5. HSM is useful for researching crystal growth rate as well as the effects of storage, particularly when it comes to heat and humidity.


    1. Polymorphism is the ability of a substance to exhibit more than one crystalline structure.
    2. Different crystalline structures are produced when structural molecules are arranged differently, a phenomenon known as polymorphism.
      The physicochemical properties of an API can vary among its different polymorphs.
    3. Polymorphisms can also be induced by drug manufacturing processes such as: Drying, Milling, Compression ,Recrystallization, Storage .Polymorphisms cannot be produced in a laboratory because of thermodynamic energy factors, but they can be produced and studied on a hot stage.
    4. HSM may be used to differentiate between polymorphs having a small difference in melting points as well as to check the stability of a polymorph at a given temperature.


    1. A cocrystal is a multicomponent solid consisting of two or more different molecules non-covalently bonded within the same crystal lattice.
    2. Cocrystals have recently attracted significant scientific attention due to their ability to modulate the physicochemical properties of API .
    3. Screening through HSM is rapid, solvent free and requires small quantities of API

Particle size distribution and characterization of an API in a tablet

    1. Particle size distribution is an important part of drug development.
    2. Particle size distribution has a significant impact on the processability of raw and finished products.
    3. Particle size distribution influences dissolution, bioavailability, and stability profiles to ensure quality, safety, and efficacy of the finished formulation.
    4. Methods exist to determine the particle size of API in tablets, but they have their own limitations, including Inability to distinguish between aggregates of tablet ingredients.

Solvates /Hydrate screening

    1. Solvates are unavoidable compounds formed during various pharmaceutical processes such as crystallization.
    2. Solvates are formed when solvent molecules are incorporated into the structure of a host compound.
    3. When water is incorporated into the host compound, these solvates are called hydrates
    4. Hot-stage microscopy can also be used for solvate/hydrate screening, as it allows visual observation of the gases generated during sample desolvation under heating