Quantifying Degree of Crystallinity

The Challenge

The measurement of residual crystallinity in final drug product is vitally important to the pharmaceutical industry. Clear andunambiguous determination of crystalline content is essential for chemical process development, formulation, stability testing and material characterization. Most traditional measurement methods, like X-ray powder diffraction (XRPD) and solid state NMR (ss-NMR), require special sample preparation for analysis that is destructive, offline and expensive. Additionally, both XRPD and ss-NMR require a large expense for initial equipment acquisition and high operating costs. While XRPD has been the gold standard for crystallinity measurement, its sensitivity is insufficient for accurate quantitative measurements at low load levels of active pharmaceutical ingredient (API).


Ondax Solutions

Ondax THz-Raman® systems extend the range of traditional Raman spectroscopy to the THz/low frequency regime, where crystal lattice modes that correlate to material structure are found and phase changes can be clearly and quickly observed. While conventional Raman may also provide phase information, the smaller Raman cross-section requires longer acquisitions times at the same laser power level, which is limiting for high throughput screening (HTS) enabled workflows. In the present example, the crystallinity content was determined using just the THz-Raman® spectra of Acetaminophen in excess excipient (lactose) at concentration ratios varying from 1 to 20% w/w.

The Ondax Solution: One Sample, One System, One Answer