(506c) NIR Spectroscopy with Multivariate Statistical Process Control for Selected Pharmaceutical Processes

Process analytical technology (PAT) is moving from research to the pharmaceutical industry and thereby providing adjuvant tools to the companies, especially for the continuous process monitoring. Thus a detailed understanding of the critical process parameters (CPPs) can be achieved following the guideline: “Quality cannot be tested into products; it has to be built in by design” [1, 2]. Here, we present two industrial use cases of near-infrared (NIR) spectroscopy with multivariate data analysis (MVDA) as a PAT tool in collaboration with G.L. Pharma GmbH.

Hot-melt extrusion is a novel method to embed drugs with a poor solubility in a polymer or wax matrix and thereby manufacturing retarded or delayed release forms. In order to determine the content homogeneity of the active pharmaceutical ingredient (API) in the extrudates, a Dynisco NIR probe was mounted at the extrusion die. Multivariate statistical process control (MSPC) was used to follow the drug content distributions within the sample matrix and for sample uniformity analysis. Furthermore, considerable spectral fluctuations indicated non-uniformly distributed ingredients due to a minimum feed rate of the implemented blender.

Fluid bed granulation is generally applied to gain uniform granules which are superior in terms of further processing, e.g. compaction and mixing, to bulk powders. The NIR spectral region shows strong water absorption signals and can therefore be used for the residual water determination. Specific NIR water signals can then be correlated with classical process data like outlet air humidity and core bed temperature. In this case the NIR spectral data was collected using a Sentronic SentroPAT FO process spectrometer which operates in the spectral region between 1100 nm and 2200 nm. The NIR probe was located at the sampler position of the granulator, about 30 cm above the ground plate.Here a batch analysis via NIR spectroscopy revealed a potential reduction of the process time by around 40 %.

[1] ICH, ICH Q8(R2), Pharmaceutical Development Part I: Pharmaceutical development

[2] ICH, ICH Q8(R2), Pharmaceutical Development Part II: Annex to pharmaceutical development