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

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Materials Science

Background:

• Solid-state properties of active pharmaceutical ingredients (APIs) are critical for drug development, influencing process and formulation design.
• Polymorphism and polymorphic stability studies are routine preformulation steps.
• Understanding solid-state transformations is essential for regulatory approval (e.g., FDA).

Purpose of the Study:

• To review the application of vibrational spectroscopies (IR, NIR, Raman) in studying solid-state transformations of APIs.
• To highlight advancements in spectroscopic techniques and their impact on understanding API solid forms.
• To focus on literature published within the last eight years.

Main Methods:

• Utilizing Infrared (IR), Near-Infrared (NIR), and Raman spectroscopies.
• In situ monitoring of phase transformations in real-time.
• Probing intermolecular interactions in various solid-state systems (e.g., cocrystals, amorphous dispersions).

Main Results:

• Vibrational spectroscopy effectively monitors transformations between crystalline and amorphous forms, hydrates/anhydrous forms, and cocrystal formation.
• Spectroscopic techniques provide insights into intermolecular interactions within API formulations.
• Advancements in instrumentation, including low-frequency Raman, have accelerated research in this field.

Conclusions:

• IR, NIR, and Raman spectroscopies are indispensable tools for characterizing API solid-state forms and transformations.
• These methods play a key role in predicting the stability of APIs and their formulations.
• The continuous development of spectroscopic techniques enhances their utility in pharmaceutical development.