The effect of process parameters on a continuous blending process monitored in-line by near-infrared spectroscopy

Area of Science:

• Pharmaceutical Manufacturing
• Process Analytical Technology (PAT)

Background:

• Continuous manufacturing ensures consistent product quality in pharmaceutical production.
• Near-infrared spectroscopy (NIRS) offers real-time monitoring of critical quality attributes in powder blends.

Purpose of the Study:

• To investigate the influence of total feed rate and impeller speed on continuous powder blending.
• To evaluate the effectiveness of NIRS for in-line monitoring of blend uniformity.

Main Methods:

• Factorial experimental design was employed to study process parameters.
• Statistical analyses including Principal Component Analysis (PCA), ANOVA Simultaneous Component Analysis (ASCA), and Partial Least Squares (PLS) regression were utilized.
• Near-infrared spectroscopy (NIRS) was used for real-time in-line assessment.

Main Results:

• Impeller speed was identified as the primary factor influencing spectral variance (55.5%) and ibuprofen concentration, attributed to powder fluidization effects.
• Both impeller speed and total feed rate showed statistically significant effects (p=0.004).
• A Partial Least Squares (PLS) regression model achieved a Root Mean Square Error of Cross-Validation (RMSECV) of 1.3% (wt/wt) for ibuprofen content prediction.

Conclusions:

• Low impeller speeds (<600 rpm) and low feed rates (<15 kg/h) optimize NIRS probe presentation for enhanced blend prediction.
• Impeller speed exerts a dominant, wavelength-dependent effect on spectral data, impacting blend uniformity.
• Optimized process parameters improve the reliability of NIRS in continuous pharmaceutical manufacturing.