Testing the Limits of a Portable NIR Spectrometer: Content Uniformity of Complex Powder Mixtures Followed by Calibration Transfer for In-Line Blend Monitoring.

Tibor Casian,Ioan Tomuta,Sonia Iurian,Alina Porfire,Valentin Toma,Alexandru Gavan,Rares Stiufiuc

doi:10.3390/molecules26041129

Tibor Casian, Ioan Tomuta + Show 5 more

Open Access

https://doi.org/10.3390/molecules26041129

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Abstract

(1) Background: Portable NIR spectrometers gain more and more ground in the field of Process Analytical Technology due to the easy on-site flexibility and interfacing versatility. These advantages that originate from the instrument miniaturization, also come with a downside with respect to performance compared to benchtop devices. The objective of this work was to evaluate the performance of MicroNIR in a pharmaceutical powder blend application, having three active ingredients and 5 excipients. (2) Methods: Spectral data was recorded in reflectance mode using static and dynamic acquisition, on calibration set samples developed using an experimental design. (3) Results: The developed method accurately predicted the content uniformity of these complex mixtures, moreover it was validated in the entire calibration range using ±10% acceptance limits. With respect to at-line prediction, the method presented lower performance compared to a previously studied benchtop spectrometer. Regarding the in-line monitoring of the blending process, it was shown that the spectral variability-induced by dynamic acquisition could be efficiently managed using spectral pre-processing. (4) Conclusions: The in-line process monitoring resulted in accurate concentration profiles, highlighting differences in the mixing behaviour of the investigated ingredients. For the low dose component homogeneity was not reached due to an inefficient dispersive mixing.

Highlights

Blending can be considered as a critical processing step in pharmaceutical manufacturing as it directly influences the end product’s content uniformity [1]
Online measurements involve the use of samples that are diverted from the main process in order to be analysed, whereas in-line measurements use invasive or noninvasive methods for direct analysis of samples without any rerouting from the process stream [3]
In the case of this specific powder mixture, we previously demonstrated that the successful implementation of a near Infrared spectroscopy (NIR) method strongly depended on the calibration set construction and on the orthogonality transfer form concentration space to spectral space

Summary

Introduction

Blending can be considered as a critical processing step in pharmaceutical manufacturing as it directly influences the end product’s content uniformity [1]. This unit operation is applied for particulate systems such as powders, granules, capsules and tablets. Content uniformity characterization is possible through off-line, at-line, on-line or inline methods, the difference between measurements being resumed to the sample analysis location. For off-line and at-line measurements samples are removed from the process stream and are analysed at a remote location or in the near proximity of the process. Atline prediction of product composition can be achieved using multivariate calibration procedure, whereas for real time process monitoring, there are several strategies which can be divided into qualitative (calibration free) and quantitative (calibration) methods [4,5]

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