Investigation of solid phase composition on tablet surfaces by grazing incidence X-ray diffraction

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Solid-State Chemistry

Background:

• Drug substance solid-state properties significantly impact pharmaceutical product performance.
• Understanding solid-state transformations during manufacturing processes like compaction is crucial for drug development.

Purpose of the Study:

• To investigate solid-state transformations of drug substances during compaction.
• To utilize grazing incidence X-ray diffraction (GIXD) for analyzing these changes.

Main Methods:

• Three model drugs (theophylline, nitrofurantoin, amlodipine besylate) were compacted at varying pressures (100-1000 MPa).
• Tablets were analyzed using GIXD, with measurements taken before and after recrystallization.
• Depth-dependent analysis of tablet surfaces was performed.

Main Results:

• Compaction induced partial amorphization and crystal disordering in all tested drugs, generally increasing with pressure.
• These effects were most pronounced at the tablet's outer surface.
• Theophylline monohydrate showed dehydration, while nitrofurantoin and amlodipine besylate hydrates remained stable.

Conclusions:

• GIXD effectively probes depth-dependent solid-form composition in compacted tablets.
• The study provides valuable information on compaction-induced amorphization, crystal disordering, and dehydration.
• Results highlight the differential solid-state responses of various drug substances to compaction stress.