Potential of Near-Infrared Chemical Imaging as Process Analytical Technology Tool for Continuous Freeze-Drying

Abstract

Near-infrared chemical imaging (NIR-CI) is an emerging tool for process monitoring because it combines the chemical selectivity of vibrational spectroscopy with spatial information. Whereas traditional near-infrared spectroscopy is an attractive technique for water content determination and solid-state investigation of lyophilized products, chemical imaging opens up possibilities for assessing the homogeneity of these critical quality attributes (CQAs) throughout the entire product. In this contribution, we aim to evaluate NIR-CI as a process analytical technology (PAT) tool for at-line inspection of continuously freeze-dried pharmaceutical unit doses based on spin freezing. The chemical images of freeze-dried mannitol samples were resolved via multivariate curve resolution, allowing us to visualize the distribution of mannitol solid forms throughout the entire cake. Second, a mannitol-sucrose formulation was lyophilized with variable drying times for inducing changes in water content. Analyzing the corresponding chemical images via principal component analysis, vial-to-vial variations as well as within-vial inhomogeneity in water content could be detected. Furthermore, a partial least-squares regression model was constructed for quantifying the water content in each pixel of the chemical images. It was hence concluded that NIR-CI is inherently a most promising PAT tool for continuously monitoring freeze-dried samples. Although some practicalities are still to be solved, this analytical technique could be applied in-line for CQA evaluation and for detecting the drying end point.

Lyophilization of Liposomal Formulations: Still Necessary, Still Challenging

“…However, the inherent limitation of this method is that only a fraction of the vial can be monitored, and intra-vial variability is thus not taken into account [ 89 ]. More recently the use of near-infrared chemical imaging (NIR-CI) was proposed for process monitoring because it combines the chemical information from the spectral features in the NIR region with the spatial information on the constituent distribution derived from the pixel-to-pixel spectral variation [ 98 ]. NIR-CI allows to discriminate among mannitol-sucrose formulations lyophilized with different drying time, to reveal within-vial inhomogeneity in water content and to characterize the solid-state of the entire lyophilized cake with a high spatial resolution [ 98 ].…”

Systematic discovery about NIR spectral assignment from chemical structural property to natural chemical compounds

“…Near-infrared (NIR) spectroscopy is fast in process, intact to sample and friendly to environment 1 . As a process analytical technology (PAT), it is widely applied to the qualitative and quantitative analysis in agriculture and food industry 2–5 . At present, its application in the field of medicine is still a hot topic.…”

Fiberoptic-Coupled Spectrofluorometer with Array Detection as a Process Analytical Chemistry Tool for Continuous Flow Monitoring of Fluoroquinolone Antibiotics

“…e Process Analytical Technology (PAT) [10,11] was defined in 2004 by the Food and Drug Administration (FDA) to support innovation in the industry quality control. PAT has many applications in the pharmaceutical and antibiotics manufacturing [12][13][14][15][16][17][18][19][20][21][22][23][24][25], chemical [26,27], petrochemical [28], and food industries [29][30][31][32][33]. In addition, there are many recent progress in realtime monitoring of cultivations in bioreactors and cell culture process [34][35][36][37][38][39][40][41], fermentation [42,43] and biological process [44], and electrochemical [45,46] and protein purification [47].…”