Abstract
An exploratory analysis of a large representative dataset obtained in a fluidized bed drying process of a pharmaceutical powder has revealed a significant correlation of spectral intensity with granulate humidity in the whole studied range of 1091.8–2106.5 nm. This effect was explained by the dependence of powder refractive properties, and hence light penetration depth, on the water content. The phenomenon exhibited a close spectral similarity to the well-known stochastic variation of spectral intensities caused by the process turbulence (the so-called “scatter effect”). Therefore, any traditional scatter-corrective preprocessing incidentally eliminates moisture-correlated variance from the data. To preserve this additional information for a more precise moisture calibration, a time-domain averaging of spectral variables has been suggested. Its application resulted in a distinct improvement of prediction accuracy, as compared to the scatter-corrected data. Further improvement of the model performance was achieved by the application of a dynamic focusing strategy when adjusting the model to a drying process stage. Probe fouling was shown to have a minor effect on prediction accuracy. The study resulted in a considerable reduction of the root-mean-square error of in-line moisture monitoring to 0.1%, which is close to the reference method's reproducibility and significantly better than previously reported results.
Highlights
Fluidized bed drying is a common unit operation routinely performed in the pharmaceutical production of solid dosage forms
We focus on efficiently using of the whole spectral information, including both absorption and scatter-related effects of water, to improve the performance of in-line moisture monitoring
Twenty-five pilot-scale fluidized bed drying batches of a pharmaceutical powder mixture were studied by using a 256pixel diode-array TIDAS 1121 SSG NIR spectrophotometer with a wavelength range of 1091.8–2106.5 nm (J&M Analytik AG, Germany) that was equipped with the Lighthouse ProbeTM (LHP) from GEA Pharma Systems nv – Collette, Belgium (Engler et al, 2009) immersed into the process medium
Summary
Fluidized bed drying is a common unit operation routinely performed in the pharmaceutical production of solid dosage forms. In a typical batch granulation process, the drying stage immediately follows either the fluidized bed or high-shear granulation stage. It is often considered as one of the most critical steps for achieving stable product quality, i.e., for obtaining granules with desired properties at their minimal variability. A close monitoring of the residual moisture content in the process medium is necessary for any quality assurance system in granulate production. A viable alternative accepted by pharmacopeias is thermogravimetric analysis with a drying balance that determines moisture content in the sample as percentage weight loss on drying (LOD). Accurate In-line NIR-Spectroscopic Monitoring of Moisture both techniques are realized as compact desktop devices enabling the at-line analysis of samples taken from a running process
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