Low-Frequency Raman Scattering Spectroscopy as an Accessible Approach to Understand Drug Solubilization in Milk-Based Formulations during Digestion

被引:22
作者
Salim, Malinda [1 ]
Fraser-Miller, Sara J. [3 ]
Berzins, Karlis [3 ]
Sutton, Joshua J. [3 ]
Ramirez, Gisela [1 ]
Clulow, Andrew J. [1 ]
Hawley, Adrian [4 ]
Beilles, Stephane [5 ]
Gordon, Keith C. [3 ]
Boyd, Ben J. [1 ,2 ]
机构
[1] Monash Univ, Monash Inst Pharmaceut Sci, Drug Delivery Disposit & Dynam, Parkville Campus, Parkville, Vic 3052, Australia
[2] Monash Univ, Monash Inst Pharmaceut Sci, ARC Ctr Excellence Convergent Bio Nano Sci & Tech, Parkville Campus, Parkville, Vic 3052, Australia
[3] Univ Otago, Dodd Walls Ctr Photon & Quantum Technol, Dept Chem, Dunedin 9054, New Zealand
[4] ANSTO, Australian Synchrotron, SAXS WAXS Beamline, Clayton, Vic 3169, Australia
[5] Sanofi R&D, Rue Prof Blayac, F-34080 Montpellier, France
基金
澳大利亚研究理事会;
关键词
low-frequency Raman spectroscopy; drug; solubilization; in vitro digestion; X-ray scattering; milk; infant formula; IN-VITRO DIGESTION; PRECIPITATION; DELIVERY; TABLETS;
D O I
10.1021/acs.molpharmaceut.9b01149
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:885 / 899
页数:15
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