The use of near-infrared spectroscopy in the efficient prediction of a specification for the residual moisture content of a freeze-dried product.

The purpose of this study is to improve the efficiency in the search for a suitable specification for the residual moisture content in a freeze-dried product. A near-infrared spectroscopic (NIRS) method was developed for the measurement of the residual moisture content. Samples with a wide range of residual moisture contents were stored for two months at 8, 50, and 60 degrees C. Because of the non-destructive character of the NIRS method initially the residual moisture content and, subsequently, the content of the active ingredient could be measured in the same sample vials after storage. Plots of the residual moisture content against the content of the active ingredient were made for storage at 50 and 60 degrees C. For this only 69 samples were needed in the stability study for the assay determination while traditionally a five-fold of samples is needed because of the high intra-batch variability of the residual moisture content. The plots at 50 and 60 degrees C were combined with the Arrhenius relationship between degradation rate constant and temperature. The maximal allowable residual moisture content was calculated with product shelf-lives of 2 and 3 years and storage temperatures of 20, 25, and 30 degrees C, respectively.