No abstract

No abstract

The aim was to evaluate near-infrared spectroscopy for the in-line determination of the drug concentration, the polymer-drug solid-state behaviour and molecular interactions during hot-melt extrusion.Kollidon ® SR was extruded with varying metoprolol tartrate (MPT) concentrations (20, 30, and 40%) and monitored using NIR spectroscopy. A PLS model allowed drug concentration determination. The correlation between predicted and real MPT concentrations was good (R²=0.97). The predictive performance of the model was evaluated by the root mean square error of prediction, which was 1.54%. Kollidon®SR with 40% MPT was extruded at 105°C and 135°C to evaluate NIR spectroscopy for in-line polymer-drug solid state characterization.NIR spectra indicated the presence of amorphous MPT and hydrogen bonds between drug and polymer in the extrudates. More amorphous MPT and interactions could be found in the extrudates produced at 135°C than at 105°C. Raman spectroscopy, DSC and ATR FT-IR were used to confirm the NIR observations. Due to the instability of the formulation, only in-line Raman spectroscopy was an adequate confirmation tool. NIR spectroscopy is a potential PAT-tool for the in-line determination of API-concentration and for the polymer-drug solid state behaviour monitoring during pharmaceutical hot-melt extrusion.

No abstract

The aim of the present paper is to demonstrate the importance of using complementary process analyzers (PAT tools) for the process monitoring, analysis, and understanding of freeze drying. A mannitol solution was used as a model system. Raman spectroscopic, near-infrared (NIR) spectroscopic, plasma emission spectroscopic, and wireless temperature measurements (TEMPRIS) were simultaneously performed in-line and real-time during each freeze-drying experiment. The combination of these four process analyzers to monitor a freeze-drying process is unique. The Raman and NIR data were analyzed using principal component analysis (PCA) and multivariate curve resolution (MCR), while the plasma emission spectroscopic and wireless temperature measurement data were analyzed using univariate data analysis. It was shown that the considered process analyzers do not only complement but also mutually confirm each other with respect to process step end points, physical phenomena occurring during freeze drying (process understanding), and product characterization (solid state). Furthermore and most important, the combined use of the process analyzers helped to identify flaws in previous studies in which these process analyzers were studied individually. Process analyzers might wrongly indicate that some process steps are fulfilled. Finally, combining the studied process analyzers also showed that more information per process analyzer can be obtained than previously described. A combination of Raman and plasma emission spectroscopy seems favorable for the monitoring of nearly all critical freeze-drying process aspects.

No abstract

No abstract

It was concluded that injection molding can be applied successfully to develop sustained-release PEO/EC matrix tablets.