Stability test for amorphous materials in humidity controlled 96-well plates by near-infrared spectroscopy

Abstract

The purpose of this research is to apply near infrared spectrometry (NIR) with chemoinformetrics to predict the change of crystalline properties of indomethacin (IMC) amorphous under various levels of relative humidity storage conditions. Stability test for amorphous and meta-stable polymorphic forms was performed in humidity controlled the modified 96-well quartz plates containing various kinds of saturated salt solutions (0–100% of relative humidity (RH)) by NIR spectroscopy. Amorphous form was obtained melt product to pour into liquid nitrogen and after then ground. Samples were stored at 25°C in the 6-well plates at various levels of RH. The spectra of the powder samples were measured by the reflectance FT-NIR spectrometer. The second derivative spectra of form α showed specific absorption peaks at 4980, 6036, 7296 and 8616 cm−1 and that of form γ showed those at 5020, 5028, 7344, 7428 and 8436 cm−1. After storage at less than 50% RH, the peak intensities at 5020, 5028, 7344, 7428 and 8436 cm−1 of the amorphous solid increased with increasing of storage time. However, the peak intensity at 4980, 6036 and 7296 cm−1 increased at more than 50% RH. The results suggested that at lower humidity, the IMC amorphous solid transformed into form γ, but it transformed into form α at more than high humidity. It is possible that crystalline stability of the pharmaceutical preparations could be predicted by using humidity controlled 96-well plates and reflectance NIR-chemoinformetric methods.