NIR prediction of solid dosage form dissolution profile

Importance of NIR-based Dissolution Profiling

Near-infrared spectroscopy (NIRS) enables rapid, non-destructive prediction of tablet dissolution profiles, aligning with FDA’s Process Analytical Technology (PAT) and Quality by Design (QbD) frameworks. By offering real-time release data, NIRS can reduce laboratory bottlenecks in conventional dissolution testing and improve manufacturing efficiency.

Study Objectives and Overview

The primary goal was to develop and validate NIR models for predicting the dissolution kinetics of intact propranolol sustained-release tablets formulated with varying levels of acetyltributyl citrate (ATBC) plasticizer. The study compared NIR-predicted profiles against standard USP dissolution tests over 24 hours.

Methodology and Instrumentation

• Tablet Formulation: Propranolol HCl tablets (20% API) containing 0%, 6%, 8% or 10% ATBC as plasticizer, with ethylcellulose matrix.
• Dissolution Testing: USP apparatus II, 900 mL buffered media, sampling at multiple time points from 1 to 24 h to generate reference profiles.
• NIR Data Acquisition: Metrohm NIRS XDS MasterLab in transmission mode (800–1650 nm, 0.5 nm intervals, 32 co-added scans).
• Chemometric Modeling: Partial least squares (PLS1) regression with seven latent factors selected by minimization of PRESS and robustness criteria in Vision® software.

Key Results and Discussion

Calibration models for each dissolution hour achieved strong linearity (e.g., R2=0.9972 at 1 h; R2≈0.99 at 12 h and 24 h) with low prediction errors (SEC<0.32%, SEP<0.42%, SECV<0.43%). Cross-validation confirmed model robustness. Superimposed NIR predictions on measured profiles across formulations demonstrated accurate tracking of drug release influenced by plasticizer level.

Applied Instrumentation

• Metrohm NIRS XDS MasterLab with tablet tray (31-position) and NIST-traceable standards.
• Elizabeth-Hata HT-AP 18 SS-U/I rotary tablet press for batch compression.

Practical Benefits and Applications

Implementing NIR prediction of dissolution enables:

• High-throughput, non-destructive analysis of entire tablet batches in under 10 min.
• Reduced reliance on time-consuming 24-h dissolution tests.
• Real-time release monitoring for PAT compliance and faster product release decisions.

Future Trends and Opportunities

Integration of NIRS into automated manufacturing lines can support continuous processing and in-line quality control. Expansion to diverse dosage forms and enhanced chemometric strategies (e.g., deep learning) may further improve predictive accuracy and application scope.

Conclusion

The study demonstrates that NIR spectroscopy combined with PLS modeling offers a reliable, rapid approach for predicting sustained-release tablet dissolution profiles. This methodology supports PAT initiatives, decreases laboratory burden, and accelerates product release workflows.

References

1. M. Blanco et al., Non-destructive dissolution testing by NIR spectroscopy, J. Pharm. Biomed. Anal., 18(6), 2007.
2. R. Fahmy, Application of NIR Spectroscopy for Formulation Development of Sustained Release Dosage Forms, FDA Center for Veterinary Medicine, 2008.
3. R.A. Mattes et al., Near-Infrared Assay and Content Uniformity of Tablets, Pharm. Technol., 4, 2007.
4. R. Kramer, Chemometric Techniques for Quantitative Analysis, Marcel Dekker, 1998.