NMR Longitudinal Rotating Frame Relaxation Time (T 1ρ ) with a Weak Spin Locking Field as an Approach to Characterize Solid-State Active Pharmaceutical Ingredients: Proof of Concept.

Nuclear magnetic resonance (NMR) longitudinal rotating frame relaxation time (T 1ρ ), rarely used in low-field NMR, can be more effective than conventional T 1 and T 2 relaxation times to differentiate polymorphic forms of solid pharmaceuticals. This could be attributed to T 1ρ sensibility to structural and molecular dynamics that can be enhanced by changing the strength of the oscillating magnetic field ( B 1 ) of spinlock pulses. Here, we compared the capacity of T 1 , T 2 , and T 1ρ to differentiate inactive (A) and active (C) crystalline forms of the World Health Organization essential drug Mebendazole. The results showed that T 1 and T 2 values of both forms were statistically identical at 0.47 T. Conversely, T 1ρ of both forms measured with weak spinlock B 1 fields, ranging from 0.08 to 0.80 mT were statistically different in the same spectrometer. The T 1ρ also has the limit of detection to detect the presence of at least 10% of inactive A form in the active C form. Therefore, T 1ρ , measured with weak spinlock B 1 fields can be an effective, streamlined, and complementary approach for characterizing not only solid active pharmaceutical ingredients but other solid-state materials as well.