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.
Application:
- 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
- Software controlled hot stage with Temperature ramping facility. Allowing controlled heating and cooling as per rate defined.
- An optical Microscope with reflected and Transmitted light observation and allowing Bright field ,Dark field and polarized observation method.
- Image capturing facility with high frame Rate to capture image and video with temperature , date , time and micron marker stamping.
- The sample is heated on a glass slide with cover slip or without cover slip with compatible liquid so that heating is homogenous.
- Hot stage should allow controlled cooling and gas purge in chamber to allow experiment in various environmental condition.
- Hexon Hot stage have various Models to give temperature range from (-40 to 600 Deg C)
Morphology Study
- Solid- state property or morphology study of API particle
- Study Api changing shape while heating and regenerating as amorphous or crystalline while cooling.
- Melting point of API and excipients
- Real time visual observation helps understand small changes in surface which may be missed by DSC and TGA.
Amorphous/crystalline form characterization
- The amorphous form of API is preferred in the pharmaceutical industry due to their higher solubility and dissolution rates over crystalline forms
- With a hot stage microscope fitted with a polarizing filter, amorphous and crystalline forms are easily distinguishable from one another.
- Crystalline materials are known to show birefringence, while amorphous material lack birefringence , hence can easily be distinguished from crystalline compounds.
- HSM is a great tool to study the conversion of an amorphous API to crystalline form under the effect of heating
- HSM is useful for researching crystal growth rate as well as the effects of storage, particularly when it comes to heat and humidity.
Polymorphism
- Polymorphism is the ability of a substance to exhibit more than one crystalline structure.
- 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. - 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.
- 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.
Cocrystals
- A cocrystal is a multicomponent solid consisting of two or more different molecules non-covalently bonded within the same crystal lattice.
- Cocrystals have recently attracted significant scientific attention due to their ability to modulate the physicochemical properties of API .
- Screening through HSM is rapid, solvent free and requires small quantities of API
Particle size distribution and characterization of an API in a tablet
- Particle size distribution is an important part of drug development.
- Particle size distribution has a significant impact on the processability of raw and finished products.
- Particle size distribution influences dissolution, bioavailability, and stability profiles to ensure quality, safety, and efficacy of the finished formulation.
- 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
- Solvates are unavoidable compounds formed during various pharmaceutical processes such as crystallization.
- Solvates are formed when solvent molecules are incorporated into the structure of a host compound.
- When water is incorporated into the host compound, these solvates are called hydrates
- 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