Assessment of blend uniformity in a stream sampler device using Raman spectroscopy

This study describes the first implementation of Raman spectrometer in a stream sampler for the in-line moni-toring of low drug concentration in poor flowability powder blends. Raman spectra were continuously acquired as the powder blends flowed through the stream sampler operating with a paddle wheel speed of 10 RPM and used to develop the calibration models. A calibration model was developed to quantify caffeine concentration from 1.50 to 4.50% w/w using Partial Least Squares Regression (PLS-R). Three test set blends were used to assess the prediction errors of the calibration model. Caffeine concentration was predicted for the test set blends with a root mean square error of prediction of 0.21% w/w and a low bias of-0.03% w/w. The calibration model showed good prediction performance with an estimated sample mass of 83 mg. Variographic analysis demon-strated the low process variance of the real-time spectral acquisition through minimum practical error and sill values. The results showed the ability of the Raman spectrometer coupled with the stream sampler to monitor low drug concentration for poor flowability blends.

Automated summary

This study presents the implementation of Raman spectrometer in a stream sampler for real-time monitoring of low drug concentration. Raman spectra were continuously acquired as powder blends flowed through the sampler operating at a paddle wheel speed of 10 RPM and used to develop a calibration model. The calibration model based on Partial Least Squares Regression (PLS-R) accurately quantified caffeine concentration in the range of 1.50% to 4.50% w/w. Evaluation of the model using test blends showed a root mean square error of prediction of 0.21% w/w and a low bias of -0.03% w/w. Variographic analysis demonstrated low process variance of real-time spectral acquisition. The results highlight the capability of the Raman spectrometer coupled with the stream sampler for monitoring low drug concentration in poor flowability blends.