Characterization of Solid-State Complexities in Pharmaceutical Materials via Stimulated Raman Scattering Microscopy

Area of Science:

• Materials Science
• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Characterizing complex solid-state mixtures, especially those with multiple polymorphic forms of the same compound, presents significant analytical challenges.
• Established methods often lack the spatial resolution or sensitivity to fully resolve and quantify these diverse forms within a single sample.

Purpose of the Study:

• To introduce and validate a novel multimodal microscopy approach using stimulated Raman scattering (SRS) and sum frequency generation (SFG) for the characterization of complex solid-state mixtures.
• To demonstrate the capability of this technique in resolving and quantifying various solid-state forms of lactose, including crystalline and amorphous phases.

Main Methods:

• Employing stimulated Raman scattering (SRS) microscopy combined with sum frequency generation (SFG) microscopy.
• Utilizing a label-free multimodal microscopy approach for imaging and analysis.
• Applying the technique to characterize five crystalline and one amorphous form of lactose, as well as commercial pharmaceutical grades.

Main Results:

• Successfully characterized and resolved six distinct solid-state forms of lactose, including two recently defined anhydrous forms.
• Visualized the spatial distribution of these solid-state forms with submicron resolution, enabling detection of trace levels.
• Provided quantitative estimations of the solid-state compositions in various lactose products.

Conclusions:

• SRS microscopy, augmented with SFG, provides sensitive, specific, and spatially resolved solid-state characterization of complex mixtures.
• This advanced technique surpasses the capabilities of established non-spatially resolved methods for detailed solid-state analysis.
• The findings have significant implications for pharmaceutical quality control and material science research.