An investigation into the spatial distribution of moisture in freeze-dried products using NIR spectroscopy and chemical imaging

Abstract

Near-infrared spectroscopy (NIRS) is a widely accepted method of measuring moisture in pharmaceutical freeze-dried products, both during the process and in the finished products. Multiple NIR measurement approaches have been introduced to monitor product moisture in freeze-dried vials. However, the spatial moisture gradients within a vial have not been investigated in depth. Like any other point-focused process analytical technology (PAT) tool, a spectrum produced by NIRS represents an average over a given area of the product vial. Implementing a point-focused NIR on any random position without proper understanding of spatial moisture variations within the vial may severely impact the reliability of the results. The present work focuses on understanding the moisture distribution within freeze-dried vials. We performed an investigation using NIR tools, NIR chemical imaging (NIR-CI), and NIRS to understand the spatial variations in moisture on the outer surface (i.e., periphery) of the freeze-dried vials. To achieve this, the moisture distribution within individual vials was mapped using NIR images. Then, NIRS was used to determine the necessity of using multiple measurement points to produce robust models quantifying moisture inside freeze-dried products. Overall, the results confirm the non-homogenous distribution of moisture, as well as the non-uniform drying front, in the products undergoing freeze-drying. The findings from the NIRS-based partial least squares (PLS) models indicate that, to achieve reliable product/process information, measurements must be drawn from multiple measurement points on the surface of the freeze-dried products.