Abstract: The objective of this study is to evaluate Raman spectroscopy as a PAT tool for the in-line determination of the API concentration and the polymer-drug solid state during a pharmaceutical hot-melt extrusion process. For in-line API quantification, different metoprolol tartrate (MPT) - Eudragit® RLPO mixtures, containing 10, 20, 30, and 40% MPT respectively, were extruded and monitored in-line in the die using Raman spectroscopy. Two different polymer-drug mixtures were prepared to evaluate Raman spectroscopy for in-line polymer-drug solid state characterization. Mixture 1 contained 90% Eudragit® RSPO and 10% MPT, and was extruded at 140°C, hence producing a solid solution. Mixture 2 contained 60% Eudragit® RSPO and 40% MPT, and was extruded at 105°C, producing a solid dispersion. DSC analysis and ATR FT-IR were used to confirm the observations. A PLS model, regressing the MPT concentrations versus the in-line collected Raman spectra, was developed and validated, allowing real-time API concentration determination. The correlation between the predicted and real MPT concentrations of the validation samples is acceptable (R²=0.997). The predictive performance of the calibration model is rated by the root mean square error of prediction, which is 0.59%. The Raman spectra collected during extrusion of mixtures 1 and 2 provided two main observations. First, the MPT Raman peaks in the solid solution broadened compared to the corresponding solid dispersion peaks, indicating the presence of MPT in the amorphous state. Secondly, peak shifts appeared in the spectra of the solid dispersion and solid solution compared to the physical mixtures, suggesting interactions between Eudragit® RS PO and MPT, most likely hydrogen bonds. These shifts were larger in the spectra of the solid solution. DSC analysis and ATR FT-IR confirmed these observations. Raman spectroscopy is a potential PAT-tool for in-line determination of API-concentration and polymer-drug solid state during pharmaceutical hot-melt extrusion processes.