Surface and Subsurface Mass Spectrometric Analysis of Dexamethasone in Solid Pharmaceutical Dosage Forms

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Materials Science

Background:

• Understanding drug distribution in pharmaceutical formulations is crucial for efficacy and safety.
• Heterogeneity in drug distribution can arise from manufacturing processes and formulation design.
• Advanced analytical techniques are needed to visualize and quantify active pharmaceutical ingredient (API) distribution at the microscale.

Purpose of the Study:

• To investigate the three-dimensional distribution of dexamethasone (DEX) within pharmaceutical tablets.
• To correlate drug distribution patterns with different formulation strengths (0.5 mg vs. 4 mg).
• To demonstrate the utility of time-of-flight secondary ion mass spectrometry (ToF-SIMS) for pharmaceutical quality control.

Main Methods:

• Utilized time-of-flight secondary ion mass spectrometry (ToF-SIMS) with gas cluster ion beam (GCIB) sputtering for in-depth chemical imaging.
• Identified the fragmentation mechanism of dexamethasone to enable specific ion detection.
• Employed atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) for complementary surface analysis.

Main Results:

• Determined the 3D chemical distribution of dexamethasone in both surface and subsurface tablet regions.
• Revealed a continuous, extended drug distribution in 4-mg DEX formulations.
• Observed localized, distinct domains of DEX in 0.5-mg formulations, indicating formulation heterogeneity.
• Confirmed topographical features and surface composition using AFM and XPS.

Conclusions:

• Advanced mass spectrometry, specifically ToF-SIMS/GCIB, provides detailed insights into API distribution within pharmaceutical tablets.
• Dexamethasone distribution patterns vary significantly with formulation strength, highlighting potential impacts on drug performance.
• These findings offer a powerful approach for pharmaceutical manufacturing quality control and formulation optimization.