The active pharmaceutical ingredient (API) must be fully characterized by the pharmaceutical industry. Certain APIs adapt different structural forms impacting the functional behavior of the drug. Polymorphs, solvates, degree of crystallization, and salt formation all represent some of the possible structural variation of APIs.
These variations can impact how the drug is delivered and its therapeutic effectiveness. Homogenous component distribution is an essential factor in the development of formulation and processing procedures. Several manufacturing processes can change the distribution and nature of APIs so it is required to check the product after these processing steps and not just the final product.
Use of Raman Spectroscopy
Raman spectroscopy can be used to identify and verify components, as well as providing detailed information on molecular structure and chemical environments. It can also be used for distinguishing similar materials.
It is possible for Raman spectroscopy to differentiate between polymorphs, which are the same chemical compounds occurring in different crystalline forms. The polymorph will be based on the crystallization conditions and the stability of the various forms.
During processing steps certain polymorphs can convert to other forms, which is very important to note as polymorphs can vary in therapeutic effectiveness.
In certain cases, one polymorph is covered with a patent and another is not, issues with IP may arise. Raman imaging is a highly powerful analysis tool as it takes this powerful spectroscopic analysis and extends it across a sample to create sample images.
Extremely small samples can be analyzed using Raman micro-spectroscopy. The sample itself is not small in the case of pharmaceutical formulations but the API (or other components) may be present in small quantities. Single point Raman spectroscopy is excellent for providing information about a specific location on the sample, but it is not always easy to locate which areas of the sample are important or representative of the whole sample.
It is possible to use larger spot sizes to cover more of the sample, but then the spectrum becomes a convolution of many components. While it still might be possible to decipher the spectral contributions of the various components, any spatial information is lost. While using Raman imaging, a view of the whole sample is provided, while preserving spatial information proving particularly important when evaluating homogeneity and spatial distribution of components, as well as for locating lower concentration components. Raman imaging offers a large amount of spectroscopic data at a rapid speed, allowing for improved analysis efficiencies and a more statistically relevant analysis of the samples.
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This information has been sourced, reviewed and adapted from materials provided by Thermo Fisher Scientific – Materials & Structural Analysis.
For more information on this source, please visit Thermo Fisher Scientific – Materials & Structural Analysis.