Amorphous Content Determination
Crystalline substances are generally less than 100% crystalline. The crystallization process itself may already produce some amorphous solids, and subsequent processing steps (such as melt quenching, freezing and spray drying, grinding, wet granulation and so on) may destroy the original crystal structure and cause chaos. Amorphous impurities have very different physicochemical properties than when they are in a crystalline state. It makes the solid form of the drug no longer well defined, its storage stability will be reduced, and the aggregation behavior of the powder may change. Therefore, the detection, quantification, characterization and management of amorphous components play a central role in ensuring process control during the development and manufacturing stages. The commonly used methods of amorphous content determinations include X-ray powder diffraction, differential scanning calorimetry, dynamic vapor sorption and so on.
Fig.1 Quantitation of the amorphous content with thermal methods.
CD Formulation laboratories can test products of any scale, and we can provide comprehensive amorphous content determination for APIs according to related standards. Our scientists will help you to make a decision for operational and procedural conditions that can ensure the physical and chemical stability and pharmacological activity of the product to minimize potential formulation and stability issues.
Our Methods for Amorphous Content Determination
| Method | Advantages | Limitations | Limit of Detection |
| X-ray Powder Diffraction (XRPD) | Nondestructive Fast Specific Universally applicable |
Requires internal referencing; no absolute values Low sensitivity Adverse effect on accuracy by crystal size and orientation possible |
10% |
| Differential Scanning Calorimetry (DSC) | Fast Specific Only small amount of substance required Uncritical kinetics |
Limited to temperature-stable substances Low sensitivity |
10% |
| Dynamic Vapor Sorption (DVS) | Sensitivity can be high Simple sample preparation Relatively simple method setup |
Depends on hygroscopicity of the amorphous material and its tendency to recrystallize | <1% |
| Microcalorimetry (μCal) | High sensitivity Simple sample preparation |
Requires suitable crystallization kinetics | <1% |
| Solution Calorimetry (SolCal) | High sensitivity | Requires rapid dissolution | <1% |
Our Advantages
If you have a requirement about amorphous content determination services, please contact us by phone or email, our colleagues will reply to you within three working days.
References
- Savolainen M, Jouppila K, Pajamo O, et al. Determination of Amorphous Content in the Pharmaceutical Process Environment[J]. Journal of Pharmacy and Pharmacology, 2007, 59(2): 161-170.
- Yu L. Amorphous Pharmaceutical Solids: Preparation, Characterization and Stabilization[J]. Advanced Drug Delivery Reviews, 2001, 48(1): 27-42.
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