Nondestructive Spatial Dehydration Analysis of Crystalline Hydrates in Pharmaceutical Solid Dosage Forms Using Spatially Offset Low-Frequency Raman Spectroscopy

Surface-driven
isothermal dehydration of model tablets containing
citric acid monohydrate was investigated using spatially offset low-frequency
Raman spectroscopy (SOLFRS). Experiments were carried out under different
isothermal conditions (50 to 65 °C), and dehydration kinetics
were monitored ex situ by sampling the tablets at
different time points. Better SOLFRS data interpretation was facilitated
by the use of multivariate curve resolution and complementary Raman
microscopy analysis of tablet cross sections that enabled access to
detailed information on spatial dehydration characteristics within
the tablets. Additionally, theoretical characterization of Raman-active
low-energy (phonon) modes of citric acid solid-state forms was carried
out using periodic boundary density functional theory.