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.

中文翻译：

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低频拉曼散射光谱法是一种在消化过程中理解牛奶配方奶中药物溶解的简便方法。

在牛奶和基于牛奶的制剂消化过程中，能够原位监测药物溶解度和药物固态变化的技术对于预测此类制剂在改善水溶性差的药物的口服生物利用度方面的有效性非常有价值。最近，我们报道了使用低频拉曼散射光谱法（分析区域<200 cm-1）作为分析方法，使用铁喹（SSR97193）作为模型化合物，在牛奶消化过程中探查药物的增溶作用。这项研究调查了这项技术的广泛应用，以探究在体外消化过程中不存在或存在胆汁盐的情况下，牛奶中以及婴儿配方食品中其他水溶性差的药物（氟安定，鲁美汀和氯氟嗪明）的增溶行为。通过跟踪药物信号特征的主成分（PC）值的变化，使用多变量分析将与药物有关的光谱变化解释为消化时间的函数。将固体药物以悬浮形式分散在牛奶和婴儿配方食品中后，所有药物的特征低频拉曼谱带都很明显。如先前对于铁喹所观察到的，通常在制剂的消化过程中药物被溶解并且与使用小角X射线散射（SAXS）确定的行为相关。与牛奶相比，通常在婴儿配方食品中也观察到更大程度的药物溶解。但是，对于氯吡嗪明药物而言，低频拉曼散射与SAXS之间的相关性尚不清楚，这可能是由于氯吡嗪胺是一种强红色染料而引起的背景干扰，这突显了这种新方法的潜在局限性。总体而言，使用低频拉曼散射光谱可以在消化过程中对牛奶和基于牛奶的配方中的药物溶解度进行原位监测，与中段相比，通过研究该光谱区域获得的信息可以更好地了解药物溶解度。频率拉曼地区。