Application of Vibrational Spectroscopy to Study Solid-state Transformations of Pharmaceuticals

Abstract

Understanding the properties, stability and transformations of the solid-state forms of an active pharmaceutical ingredient (API) in the development pipeline is of crucial importance for process-development, formulation development and FDA approval. Investigation of the polymorphism and polymorphic stability is a routine part of the preformulation studies. Vibrational spectroscopy allows the real-time in situ monitoring of phase transformations and probes intermolecular interactions between API molecules, between API and polymer in amorphous solid dispersions or between API and coformer in cocrystals or coamorphous systems and thus plays a major role in efforts to gain a predictive understanding of the relative stability of solid-state forms and formulations. Infrared (IR), near-infrared (NIR) and Raman spectroscopies, alone or in combination with other analytical methods, are important tools for studying transformations between different crystalline forms, between the crystalline and amorphous form, between hydrate and anhydrous form and for investigating solid-state cocrystal formation. The development of simple-to-use and cost-effective instruments on the one hand and recent technological advances such as access to the low-frequency Raman range down to 5 cm-1, on the other, have led to an exponential growth of the literature in the field. This review discusses the application of IR, NIR and Raman spectroscopies in the study of solid-state transformations with a focus on the literature published over the last eight years.

Pharmaceutical Cocrystal Formation of Pyrazinamide with 3-Hydroxybenzoic Acid: A Terahertz and Raman Vibrational Spectroscopies Study

“…Raman spectroscopy has become a crucial and mainstream measurement technique to provide specific structural fingerprint information by which different materials could be exclusively characterized at the micro-molecular level and also identified in various chemical processes [26]. Experimental Raman spectra of the two cocrystals between PZA and 3-hBA are shown in Figure 5d,e, and it can be easily seen that both solvent cocrystal and grinding cocrystal are almost the same as each other.…”