Fast Compressive Raman Imaging of Polymorph Molecules and Excipients in Pharmaceutical Tablets

Area of Science:

• Spectroscopy
• Chemical Imaging
• Materials Science

Background:

• Pharmaceutical analysis requires accurate identification and characterization of active pharmaceutical ingredients (APIs).
• Polymorphism in APIs can significantly impact drug efficacy and stability, necessitating robust quality control methods.
• Current imaging techniques may lack the speed and specificity required for real-time pharmaceutical quality control.

Purpose of the Study:

• To implement a near-infrared (NIR) compressive Raman imaging system for rapid chemical analysis.
• To demonstrate the system's capability in detecting and imaging polymorphic forms of APIs within pharmaceutical tablets.
• To establish a foundation for fast pharmaceutical quality control using advanced imaging techniques.

Main Methods:

• Development of a near-infrared compressive Raman imaging system utilizing a digital micromirror device (DMD) and a single-pixel detector.
• Application of chemometric analysis for spectral data processing and image reconstruction.
• Acquisition of chemical images of pharmaceutical tablets containing known mixtures of APIs and excipients.

Main Results:

• Successful detection and chemical imaging of active pharmaceutical ingredients exhibiting polymorphism in compact pharmaceutical tablets.
• Demonstration of high-speed imaging with a pixel dwell time of 2.5 ms (0.5 ms per species) for a mixture of clopidogrel polymorphs and excipients.
• Validation of the system's ability to differentiate and map different chemical species within solid dosage forms.

Conclusions:

• The developed NIR compressive Raman imaging system offers a fast and effective method for pharmaceutical analysis.
• This technology provides a pathway for rapid quality control of pharmaceutical tablets, including the assessment of API polymorphism.
• Compressive Raman imaging presents a promising tool for advancing pharmaceutical manufacturing and quality assurance processes.