Fluorescence-Detected Mid-Infrared Photothermal Microscopy

Area of Science:

• Spectroscopy and Microscopy
• Materials Science
• Pharmaceutical Sciences

Background:

• Amorphous solid dispersions (ASDs) are crucial for enhancing drug solubility and bioavailability.
• Phase separation in ASDs can significantly impact drug dissolution kinetics and stability.
• Characterizing the localized chemical composition within inhomogeneous ASDs remains challenging.

Purpose of the Study:

• To introduce and validate fluorescence-detected photothermal infrared (F-PTIR) microscopy for analyzing ASDs.
• To demonstrate the capability of F-PTIR for label-free chemical characterization of microdomains within ASDs.
• To investigate the impact of water sorption on the phase behavior of model ASDs.

Main Methods:

• Development of instrumentation for fluorescence-detected photothermal infrared (F-PTIR) microscopy.
• Utilizing temperature-dependent changes in fluorescence quantum efficiency to detect localized infrared absorption.
• Applying F-PTIR to model systems (polyethylene glycol, silica gel) and ritonavir/polyvinylpyrrolidone-vinyl acetate (PVPVA) ASDs.

Main Results:

• F-PTIR microscopy provides high spatial resolution for infrared spectroscopic analysis, dictated by fluorescence imaging.
• Label-free F-PTIR was achieved using intrinsic autofluorescence of tryptophan and protein microparticles.
• Characterization of inhomogeneous ritonavir/PVPVA ASDs revealed the formation of drug-rich domains upon water sorption, supporting phase separation.

Conclusions:

• F-PTIR microscopy is a powerful tool for label-free chemical characterization of microscale composition in ASDs.
• Water sorption induces phase separation in ritonavir/PVPVA ASDs, leading to drug-rich domains.
• Understanding phase separation in ASDs is critical for optimizing drug delivery and stability.