Characterization of pharmaceutically relevant materials at the solid state employing chemometrics methods

Area of Science:

• Pharmaceutical Sciences
• Analytical Chemistry
• Chemometrics
• Process Analytical Technology (PAT)

Background:

• Building quality into pharmaceutical products requires deep understanding of materials and manufacturing processes.
• Rapid, efficient, and versatile analytical methods are crucial for real-time process monitoring and control.
• Solid dosage form manufacturing demands reliable insights into process performance for quality assurance.

Purpose of the Study:

• To review successful applications of chemometrics combined with analytical techniques for pharmaceutical solid-state analysis.
• To highlight how these methods address analytical challenges throughout the manufacturing and control processes.
• To discuss the integration of chemometrics-assisted methods within the Process Analytical Technology (PAT) framework.

Main Methods:

• Integration of multivariate chemometrics algorithms with analytical techniques such as vibrational spectroscopies (Raman, MIR, NIR), UV-Vis, and X-ray powder diffraction.
• Application of these combined methods for qualification and quantification tasks in pharmaceutical manufacturing.
• Utilizing chemometrics for chemical imaging to extract spatial and compositional information.

Main Results:

• Successful characterization and evaluation of pharmaceutical materials in the solid state.
• Monitoring of crystallization processes, supramolecular drug associations (co-crystals, co-amorphous, salts), crystal morphology, particle size, solubility, and dissolution.
• Identification and quantification of active pharmaceutical ingredients in complex mixtures, assessment of drug stability, detection of adulterated medicines, and analysis of solid-state transformations.

Conclusions:

• Chemometrics-assisted analytical methods are vital for ensuring quality in bulk active pharmaceutical ingredients and final drug products.
• These integrated approaches support the modern Process Analytical Technology (PAT) paradigm for controlled manufacturing.
• The review demonstrates the broad utility of chemometrics in solving diverse analytical problems in the pharmaceutical industry.