Detecting Low-Level Crystallinity in ASD-like Samples Using ssNMR Techniques

This study compares solid-state NMR (SSNMR), XRPD, and DSC for detecting low-level crystallinity in spray-dried dispersion (SDD) systems using triamcinolone as a model compound. ¹⁹F and ¹³C SSNMR, particularly when combined with ¹H T_1rho filtering, enable highly specific separation of amorphous and crystalline signals and reveal crystalline impurities at levels as low as 0.3%—well below the detection limits of XRPD or DSC. The results demonstrate that SSNMR provides superior sensitivity, form specificity, and excipient/API signal resolution, offering a robust technique for characterizing crystallization in ASD-like formulations without requiring extensive experimental time.