Time domain NMR for polymorphism characterization: Current status and future perspectives

Area of Science:

• Solid-state chemistry
• Pharmaceutical sciences
• Analytical chemistry

Background:

• Polymorphism, the existence of multiple crystal forms of a compound, significantly impacts physicochemical and pharmacokinetic properties of Active Pharmaceutical Ingredients (APIs).
• Accurate characterization of API solid-state properties is crucial for drug development and ensuring final product efficacy.
• Traditional characterization methods include X-Ray Diffraction, Differential Scanning Calorimetry, and various spectroscopic techniques.

Purpose of the Study:

• To provide an overview of current advancements in Time Domain Nuclear Magnetic Resonance (TD-NMR) for polymorphism assessment in pharmaceutical products.
• To highlight the growing application and advantages of TD-NMR in evaluating API solid-state characteristics.
• To compare various TD-NMR applications for API solid-state characterization and suggest future research directions.

Main Methods:

• Review of recent literature (past five years) focusing on Time Domain Nuclear Magnetic Resonance (TD-NMR) applications for solid-state characterization.
• Analysis of TD-NMR's utility in evaluating polymorphism in Active Pharmaceutical Ingredients (APIs).
• Comparison of TD-NMR with conventional high-field NMR devices for industrial applicability.

Main Results:

• TD-NMR is increasingly reported for evaluating polymorphism in APIs, demonstrating growing interest in this technique.
• TD-NMR offers advantages over high-field NMR, including smaller equipment size and shorter measurement times, making it suitable for industrial applications.
• The study compares diverse TD-NMR applications for API solid-state characterization.

Conclusions:

• TD-NMR is a compelling and industrially convenient technique for assessing polymorphism in pharmaceutical APIs.
• Further research and application of TD-NMR are encouraged for robust solid-state characterization in drug development.
• TD-NMR provides a valuable alternative or complementary method to existing techniques for polymorphism analysis.