In Operando Analysis of Milk-Based Oral Formulations during Digestion Using Synchrotron Small-Angle X-ray Scattering Coupled to Low-Frequency Raman Spectroscopy.

Abstract

A low-frequency Raman (LFR) probe was coupled to an in-line small-angle X-ray scattering (SAXS) beamline to test the capabilities of a combinatory approach for the determination of lipid and drug behavior during the enzymatic lipolysis of milk-based oral formulations. Cinnarizine was used as the model drug, and its solubilization dynamics as well as its potential impact on the supramolecular structures formed by the digestion products of bovine milk were evaluated from the perspective of both techniques. The SAXS data were superior in distinguishing various liquid crystalline assemblies formed during the digestion process, with LFR providing complementary information regarding the formation of calcium soaps. On the other hand, studying changes in the LFR domain allowed the differentiation of drug solubilization and precipitation; processes that were less clear from the X-ray scattering data. Given the relative simplicity of the combined experimental setup, these results highlight the advantages that the combination of the two techniques can provide for understanding and developing new lipid-based formulations and will help to translate the results obtained at synchrotron facilities to routine analysis procedures in laboratory/industry-based environments.