In this study, we employed stimulated Raman scattering (SRS) microscopy, augmented with sum frequency generation, to characterize complex solid-state mixtures, containing many solid-state forms of the same compound, for the first time. Five crystalline forms and one amorphous form of lactose were characterized and resolved, including two more recently defined anhydrous solid-state forms. Additionally, the complex solid-state character of several commercially available pharmaceutical tableting and inhalation grades of lactose was profiled. The advanced multimodal label-free microscopy method enabled visualization of the distribution of the solid-state forms with submicron spatial resolution, including the detection of trace levels. In addition, quantitative solid-state compositions of the lactose products were estimated. Overall SRS microscopy allows sensitive and specific spatially resolved solid-state characterization of complex mixtures, beyond what is possible with established (nonspatially resolved) characterization methods.

Biomedicum Imaging Unit University of Helsinki Helsinki 00014 Finland

Department of Chemistry University of Helsinki Helsinki 00014 Finland

Dodd Walls Centre for Photonic and Quantum Technologies and Department of Chemistry University of Otago Dunedin 9054 New Zealand

Drug Research Program Division of Pharmaceutical Chemistry and Technology University of Helsinki Helsinki 00014 Finland

Orion Corporation Espoo 02200 Finland

Zentiva k s U K abelovny 130 Prague 10 10237 Czech Republic

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