Kinetic Model of Diclofenac Degradation Developed Using Multivariate Curve Resolution Method

Area of Science:

• Pharmaceutical Science
• Chemical Kinetics
• Spectroscopy

Background:

• Understanding the long-term stability of pharmaceuticals like Diclofenac is crucial for ensuring drug efficacy and patient safety.
• Natural aging, as opposed to accelerated aging, provides a more realistic assessment of drug degradation under typical storage conditions.
• Near-infrared (NIR) spectroscopy is a valuable non-destructive technique for analyzing chemical changes in pharmaceutical formulations.

Purpose of the Study:

• To develop a kinetic model for the natural long-term aging of Diclofenac substance and intact tablets.
• To propose a generic degradation mechanism for Diclofenac under natural aging conditions.
• To analyze Diclofenac tablets packaged in blister packs, reflecting real-world pharmaceutical presentation.

Main Methods:

• Acquisition of near-infrared (NIR) spectra from fresh and degraded Diclofenac pure substance and intact tablets.
• Application of Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS) in its soft version.
• Kinetic modeling of spectral data to elucidate degradation pathways and kinetics.

Main Results:

• A global kinetic model for Diclofenac degradation was proposed.
• Approximations of the NIR spectra for intermediate and product species were obtained.
• Rate constants for the degradation process were estimated.
• Analysis of Diclofenac tablets in blister packs provided practical insights into pharmaceutical stability.

Conclusions:

• The study successfully modeled the natural aging of Diclofenac, offering a realistic degradation mechanism.
• The methodology provides a framework for assessing the stability of pharmaceuticals without accelerated aging techniques.
• Findings are directly applicable to the pharmaceutical industry, particularly concerning packaged drug products.