This work presents the evaluation of a co-processed material for high-load dose formulations and its real-time monitoring by near-infrared (NIR) spectroscopy at the tablet press feed frame. The powder and tableting properties of co-processed material blends were evaluated and compared to the blend of the individual excipients. The formulations with the co-processed material showed excellent flow properties and were superior to the physical blend of individual excipients. Two NIR spectroscopic methods were developed to monitor ibuprofen concentration between 40.0 and 60.0% w/w, one method using a co-processed material as the main excipient and the other using the blend of the individual excipients. The NIR spectra were obtained while the powder blends flowed within a three-chamber feed frame from a Fette 3090 tablet press. The NIR spectroscopic method with the co-processed material presented better performance with significantly lower prediction error. Variographic analysis demonstrated that using the co-processed material considerably reduces the sampling and analytical errors in the in-line determination of ibuprofen. The authors understand that this is the first study where the sampling errors are evaluated as a function of the excipients used in the pharmaceutical formulation. This study demonstrated that selecting a suitable excipient for the formulation helps optimize the manufacturing process, reducing the magnitude of the total measurement error.