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

Abstract

Polymorphism is the ability of a compound to exist in multiple crystal forms while maintaining the same chemical composition. This phenomenon is reflected in different solid-state physicochemical properties due to variations in structural energy and the degree of lattice disorder. The pharmaceutical industry places significant emphasis on thoroughly characterizing polymorphism in Active Pharmaceutical Ingredients (APIs) because of its impact on the pharmacokinetic properties on the final medicine product. Standard characterization techniques are well documented in pharmacopeias and by international agencies. These techniques, whether applied individually or in combination, include crystallography (X-Ray Diffraction), thermal analysis (Differential Scanning Calorimetry), and various forms of spectroscopy, such as Near-Infrared, Raman, and solid-state Nuclear Magnetic Resonance (NMR). Analyzing NMR applications for solid-state characterization over the past five years, there has been a growing number of reports on the use of Time Domain NMR (TD-NMR) to evaluate polymorphism on APIs. Due to the increasing interest in this compelling technique, this study provides an overview of the current advancements in TD-NMR for polymorphism assessment in pharmaceutical products. Compared to high-field devices, TD-NMR has proven to be more convenient to industrial applications due to its smaller equipment size and shorter measurement times. This mini-review compares various applications of TD-NMR for API solid-state characterization and offer guidance for future research in this area.

Keywords: Active Pharmaceutical Ingredient; NMR; Polymorphism; Relaxometry.