Quality by design, part I: application of NIR spectroscopy to monitor tablet manufacturing process

Area of Science:

• Pharmaceutical Technology
• Analytical Chemistry
• Spectroscopy

Background:

• Tablet manufacturing requires robust quality control measures.
• Near-infrared (NIR) spectroscopy offers a rapid, non-destructive analytical approach.
• Chemometrics provides tools for analyzing complex spectral data.

Purpose of the Study:

• To develop and validate chemometric models using NIR spectroscopy for monitoring key tableting parameters.
• To assess the predictive capability of NIR spectroscopy for content uniformity, compression force, and crushing strength of orbifloxacin tablets.

Main Methods:

• Orbifloxacin tablets were manufactured with varying drug content and compression forces.
• Tablets were analyzed using ultraviolet (UV) and NIR spectroscopy.
• Chemometric models, including Principal Component Analysis (PCA), Multiple Linear Regression (MLR), and Partial Least Squares (PLS), were developed.
• Model performance was evaluated using Standard Error of Calibration (SEC) and Standard Error of Prediction (SEP).

Main Results:

• Partial Least Squares (PLS) models demonstrated superior performance compared to Multiple Linear Regression (MLR) models.
• The best-fit PLS models achieved low SEC and SEP values for predicting content uniformity (1.13/1.36 mg), compression force (69.86/59.48 lb), and crushing strength (0.55/0.57 kP).
• PCA effectively identified regular and capped tablet breakage patterns.

Conclusions:

• NIR spectroscopy, coupled with multivariate modeling, is a viable and reliable technique for real-time monitoring of pharmaceutical tablet production.
• This approach enables non-destructive and rapid prediction of critical quality attributes like content uniformity, compression force, and crushing strength.
• The developed models offer a significant advancement in quality control for orbifloxacin tablet manufacturing.