This study validates the feasibility of using pulsed nuclear magnetic resonance (NMR) as a novel technique for estimating relative amounts of crystalline and amorphous phases. The amounts of crystalline and amorphous ursodeoxycholic acid (UDCA) were determined using three methods: powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and pulsed NMR. The methods' analytical validation covered the parameters linearity, limit of detection (LOD), limit of qualification (LOQ), and repeatability. The UDCA calibration curve for DSC exhibited greater linearity (R²=0.9938) than for PXRD (R²=0.9468). LOD and LOQ values of DSC were 2.1% and 7.6% (w/w, crystalline phase), respectively. In contrast, the pulsed NMR method enabled quantification of the amorphous component amount based on the spin-spin relaxation time and intensity of free induction decay curves derived from the amorphous phase. Analytical validation of the pulsed NMR technique exhibited high linearity, especially using the solid echo pulse sequence (R²=0.9978) ; moreover, LOD and LOQ values were 3.5% and 10.6% (w/w, amorphous phase), respectively. Amorphous UDCA was accurately and precisely quantified by pulsed NMR as a non-destructive and rapid analysis technique, thus indicating that this method is a powerful tool for quantifying crystalline and amorphous contents of small-molecule drugs.

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