GMP Amorphous content detection, quantification and method validation.
During the manufacture and processing of active drug substances, amorphous regions or defects may be induced due to the shear physical forces applied (such as milling or impaction, compression, attrition, etc). Although the percentage of amorphous content introduced in this way is usually low (in the order of ~ 1% w/w), its location primarily on the surface of what are usually small particles gives it a disproportionate control on the properties of the material. This can dramatically change the physical properties of the compound, such as altering the flow properties, specific surface area, compressibility and dissolution rate etc.
It is therefore of the utmost importance to strictly monitor the processing of drug substances with regards to the generation of amorphous material, as well obtain a comprehensive understanding of its physical and chemical stability.
Typical studies include
- Selection of the best method for your API for the quantification of amorphous content (isothermal nanocalorimetery, solution calorimetery, Raman sepctroscopy, NIR spectroscopy or others)
- Use the optimum method for the quantification of amorphous content (down to 0.5 %), if required providing full method validation with qualified GMP instruments
- Identification and monitoring of the glass transition temperature (Tg)
- Determine relaxation times as a function of temperature and relative humidity
- Determine amorphous stability with regards to hygroscopic behaviour
- Monitor recrystallisation behaviour as a function of temperature, time or relative humidity
At Pharmaterials we do not believe in one method being best for every sample. We use our decades of experience in multiple methods in order to find and use the best science and solution for you.
Check out the methods we can offer
Prof Buckton's amorphous content publications
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