The Application of Vibrational Spectroscopy in Studies of Structural Polymorphism of Drugs

Structural polymorphism of active pharmaceutical ingredients (APIs) is a common phenomenon being a subject of continuous investigation. Depending on the crystalline or amorphous form, APIs may have different physicochemical properties, including solubility, which ultimately affects the various concentrations of the tested polymorphic forms of the drug in body fluids. Currently, the different scanning calorimetry and X-ray diffraction are the methods of choice in studies of structural polymorphism of drugs. Three vibrational spectroscopic techniques namely: Fouriertransform infrared, Attenuated total reflection and Raman spectroscopy may be indicated as alternative, non-destructive, fast and cheap methods. In addition, the theoretical approach based on quantum-chemical calculations and chemometrics solutions is considered an important support in identification of various polymorphic forms of drugs by determination of positions of bands and their intensities in analyzed samples. In the first part of this chapter, we will focus on description of the differences in the structure of crystalline and amorphous forms of APIs, their pharmaceutical implications and characteristic of vibrational techniques that can be used in studies on polymorphism of drugs. In the second part, we will present the most important examples of the application of the above mentioned vibrational techniques to identify polymorphic and amorphous forms of APIs with different profiles of pharmacological activity and conventional and innovative excipients. Finally, the advantages and limitations of vibrational spectroscopy to study the structural polymorphism of drugs will be indicated and discussed.

Keywords: Active Pharmaceutical Ingredients, Amorphous form, Excipients, Pharmaceutical Analysis, Pharmaceuticals, Physicochemical properties, Polymorphous forms.