Synchrotron Radiation Microcomputed Tomography Guided Chromatographic Analysis for Displaying the Material...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• The 3D microstructure and spatial distribution of active pharmaceutical ingredients (APIs) and excipients in solid dosage forms are understudied.
• Understanding these microstructural relationships is crucial for developing effective drug delivery systems.

Purpose of the Study:

• To investigate the 3D microstructure and material distribution within multiple-unit pellet system (MUPS) tablets.
• To establish synchrotron radiation X-ray microcomputed tomography (SR-μCT) combined with chromatography for detailed analysis.
• To facilitate the design of quantitative models for drug delivery systems.

Main Methods:

• Utilized synchrotron radiation X-ray microcomputed tomography (SR-μCT) for 3D structural elucidation.
• Employed liquid chromatography coupled to mass spectrometry (LC-MS) or evaporative light-scattering detector (LC-ELSD) for chemical analysis.
• Quantified material distribution within validated microregions of theophylline MUPS tablets.

Main Results:

• MUPS tablets were characterized into three structural domains: matrix layer (ML), protective cushion layer (PCL), and pellets (PL).
• The protective cushion layer (PCL) showed higher proportions of theophylline, sucrose, and diethyl phthalate compared to the matrix layer (ML).
• Glyceryl monostearate was a major component of the protective cushion layer (PCL).

Conclusions:

• Microstructural characterization combined with zonal chemical determination offers a novel approach for quality assessment.
• This method provides unprecedented insight into the constituent layers of drug delivery systems.
• The findings support the development of advanced quantitative models for drug delivery systems.