Application of process analytical technology in tablet process development using NIR spectroscopy: blend uniformity,...

Area of Science:

• Pharmaceutical manufacturing
• Analytical chemistry
• Process analytical technology (PAT)

Background:

• Traditional methods for monitoring tabletting processes can be time-consuming and may not provide real-time data.
• Near-infrared (NIR) spectroscopy offers a non-destructive, rapid analytical approach for in-process monitoring.
• Implementing PAT is crucial for ensuring consistent product quality and optimizing manufacturing efficiency.

Purpose of the Study:

• To apply Near-infrared (NIR) spectroscopy as a Process Analytical Technology (PAT) for monitoring multiple stages of the tabletting process.
• To evaluate NIR spectroscopy for assessing blend homogeneity, tablet content uniformity, and coating thickness.
• To develop and validate NIR-based models for accurate quantitative analysis during pharmaceutical manufacturing.

Main Methods:

• Utilized a diode-array spectrometer for blend uniformity monitoring with a calibration-free model.
• Employed a Fourier-transform spectrometer for content uniformity and coating thickness analysis using calibration-based models.
• Investigated both reflectance and transmission spectra for coating thickness prediction.

Main Results:

• Blend homogeneity was achieved within 2 minutes post-delumping, with relative standard deviation (R.S.D.) between 1.0% and 2.5%.
• Content uniformity prediction showed root mean square error of cross-validation (RMSEP) of 1.94% for uncalibrated pressures and 1.48% for calibrated pressures.
• Reflectance-based models provided more accurate coating thickness predictions than transmission-based models, with comparable results to reference measurements.

Conclusions:

• NIR spectroscopy is a viable PAT tool for real-time monitoring of pharmaceutical tabletting.
• The developed NIR methods accurately assess critical quality attributes like blend uniformity, content uniformity, and coating thickness.
• NIR spectroscopy enables efficient process control and quality assurance throughout the tabletting process.