Crystallization Kinetics of an Amorphous Pharmaceutical Compound Using Fluorescence-Lifetime-Imaging Microscopy

Area of Science:

• Pharmaceutical Science
• Materials Science
• Analytical Chemistry

Background:

• Amorphous drug formulations offer higher dissolution rates, increasing their importance in the pharmaceutical industry.
• Characterization of amorphous solid states is crucial for drug development and quality control.
• Solid-state transformations, like crystallization, can impact drug efficacy and stability.

Purpose of the Study:

• To investigate the utility of fluorescence-lifetime-imaging microscopy (FLIM) for monitoring the crystallization of amorphous indomethacin.
• To differentiate between amorphous and crystalline forms of indomethacin using time-resolved fluorescence.
• To quantitatively analyze the crystallization process using FLIM data.

Main Methods:

• Utilized fluorescence-lifetime-imaging microscopy (FLIM) to analyze indomethacin.
• Differentiated solid indomethacin forms (amorphous, γ-crystalline, α-crystalline) based on time-resolved fluorescence decay.
• Monitored amorphous indomethacin crystallization at 60 °C over 10 days using FLIM.
• Analyzed crystallization progress via changes in FLIM images, fluorescence decay curves, and lifetime amplitudes.

Main Results:

• Distinct fluorescence lifetimes and amplitudes were identified for amorphous, γ-crystalline, and α-crystalline indomethacin.
• FLIM successfully detected and visualized the crystallization of amorphous indomethacin over time.
• Quantitative analysis of crystallization progress was achieved using fluorescence-lifetime amplitudes and distributions.
• Changes in fluorescence-lifetime distribution provided insights into reaction kinetics.

Conclusions:

• FLIM is a sensitive and non-destructive method for monitoring solid-state transformations in fluorescent pharmaceutical compounds.
• FLIM enables detailed characterization and analysis of amorphous drug crystallization.
• The technique offers valuable data for understanding and controlling drug formulation stability and performance.