Dataset Information

Application of Low-Frequency Raman Scattering Spectroscopy to Probe in Situ Drug Solubilization in Milk during Digestion.

ABSTRACT: We have recently shown that real-time monitoring of drug solubilization and changes to solid state of the drug during digestion of milk can be achieved using synchrotron small-angle X-ray scattering. A complementary laboratory-based method to explore such changes is low-frequency Raman spectroscopy, which has been increasingly used to characterize crystalline drugs and their polymorphs in powders and suspensions. This study investigates the use of this technique to monitor in situ drug solubilization in milk during the process of digestion, using a lipolysis model/flow-through configuration identical to that used previously for in situ synchrotron small-angle X-ray scattering studies. An antimalarial drug, ferroquine (SSR97193), was used as the model drug for this study. The Raman spectra were processed using multivariate analysis to extract the drug signals from the milk digestion background. The results showed disappearance of the ferroquine peaks in the low-frequency Raman region (<200 cm^-1) after approximately 15-20 min of digestion when milk fat was present in the system, which indicated drug solubilization and was in good agreement with the in situ small-angle X-ray scattering measurements. This proof-of-concept study therefore suggests that low-frequency Raman spectroscopy can be used to monitor drug solubilization in a complex digesting milk medium because of the unique vibrational modes of the drug crystal lattices.

SUBMITTER: Salim M

PROVIDER: S-EPMC6503463 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Application of Low-Frequency Raman Scattering Spectroscopy to Probe in Situ Drug Solubilization in Milk during Digestion.

Salim Malinda M Fraser-Miller Sara J SJ Sutton Joshua J JJ Be Rziņš Ka Rlis KR Hawley Adrian A Clulow Andrew J AJ Beilles Stéphane S Gordon Keith C KC Boyd Ben J BJ

The journal of physical chemistry letters 20190423 9

We have recently shown that real-time monitoring of drug solubilization and changes to solid state of the drug during digestion of milk can be achieved using synchrotron small-angle X-ray scattering. A complementary laboratory-based method to explore such changes is low-frequency Raman spectroscopy, which has been increasingly used to characterize crystalline drugs and their polymorphs in powders and suspensions. This study investigates the use of this technique to monitor in situ drug solubiliz ...[more]

PMID: 31013099

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Project description:Techniques enabling in situ monitoring of drug solubilization and changes in the solid-state of the drug during the digestion of milk and milk-based formulations are valuable for predicting the effectiveness of such formulations in improving the oral bioavailability of poorly water-soluble drugs. We have recently reported the use of low-frequency Raman scattering spectroscopy (region of analysis <200 cm-1) as an analytical approach to probe solubilization of drugs during digestion in milk using ferroquine (SSR97193) as the model compound. This study investigates the wider utilization of this technique to probe the solubilization behavior of other poorly water-soluble drugs (halofantrine, lumefantrine, and clofazimine) in not only milk but also infant formula in the absence or presence of bile salts during in vitro digestion. Multivariate analysis was used to interpret changes to the spectra related to the drug as a function of digestion time, through tracking changes in the principal component (PC) values characteristic to the drug signals. Characteristic low-frequency Raman bands for all of the drugs were evident after dispersing the solid drugs in suspension form in milk and infant formula. The drugs were generally solubilized during the digestion of the formulations as observed previously for ferroquine and correlated with behavior determined using small-angle X-ray scattering (SAXS). A greater extent of drug solubilization was also generally observed in the infant formula compared to milk. However, in the case of the drug clofazimine, the correlation between low-frequency Raman scattering and SAXS was not clear, which may arise due to background interference from clofazimine being an intense red dye, which highlights a potential limitation of this new approach. Overall, the in situ monitoring of drug solubilization in milk and milk-based formulations during digestion can be achieved using low-frequency Raman scattering spectroscopy, and the information obtained from studying this spectral region can provide better insights into drug solubilization compared to the mid-frequency Raman region.

Dataset Information

Application of Low-Frequency Raman Scattering Spectroscopy to Probe in Situ Drug Solubilization in Milk during Digestion.

Publications

Application of Low-Frequency Raman Scattering Spectroscopy to Probe in Situ Drug Solubilization in Milk during Digestion.

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