Hot-stage microscopy for determination of API fragmentation: comparison with other methods

Area of Science:

• Pharmaceutical Science
• Materials Science

Background:

• Active pharmaceutical ingredient (API) fragmentation is a known phenomenon in tablet manufacturing.
• Existing analytical tools for investigating API fragmentation are limited.

Purpose of the Study:

• To investigate the real fragmentation of tadalafil particles in model tablets using hot-stage microscopy.
• To evaluate the influence of compaction pressure on tadalafil fragmentation.
• To compare hot-stage microscopy with spectral imaging for fragmentation analysis.

Main Methods:

• Model tablets containing tadalafil and excipients were prepared under varying compaction pressures (5–35 kN).
• Hot-stage microscopy was employed to observe real-time particle fragmentation.
• Morphology, spectral imaging, and analysis of plastic and elastic energies were used as supporting methods.

Main Results:

• Hot-stage microscopy demonstrated clear tadalafil fragmentation with increasing compaction pressure.
• Fragmentation patterns correlated well with calculated plastic and elastic energies.
• Spectral imaging proved inaccurate, primarily measuring agglomerates instead of individual particles.

Conclusions:

• Hot-stage microscopy is a suitable and reliable in vitro method for assessing API fragmentation in solid dosage forms.
• This technique provides valuable insights into particle behavior during tablet compaction.
• The findings will aid pharmaceutical scientists in predicting and managing API fragmentation.