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Abstract：
Advanced drug delivery systems (ADDS) are widely explored to overcome poor aqueous solubility of orally administered drugs. However, the prediction of their in vivo performance is challenging, as in vitro models typically do not capture the interplay between processes occurring in the gut. In additions, different models are used to evaluate the different systems. We therefore present a method that allows monitoring of luminal processing (dissolution, digestion) and its interplay with permeation to better inform on the absorption of felodipine formulated as ADDS. Experiments were performed in a µFLUX-apparatus, consisting of two chambers, representing the intestinal and serosal compartment, separated by Caco-2 monolayers. During dissolution-digestion-permeation experiments, ADDS were added to the donor compartment containing simulated intestinal fluid and immobilized lipase. Dissolution and permeation in both compartments were monitored using in situ UV-probes or, when turbidity interfered the measurements, with HPLC analysis. The method showed that all ADDS increased donor and receiver concentrations compared to the condition using crystalline felodipine. A poor correlation between the compartments indicated the need for an serosal compartment to evaluate drug absorption from ADDS. The method enables medium-throughput assessment of: (i) dynamic processes occurring in the small intestine, and (ii) drug concentrations in real-time.
摘要：
先进的药物递送系统(ADDS)被广泛地探索以克服口服给药的药物的差的水溶性。然而,对它们体内性能的预测是具有挑战性的，因为体外模型通常不能捕获在肠道中发生的过程之间的相互作用。Inadditions,使用不同的模型来评估不同的系统。因此，我们提出了一种允许监测管腔处理(溶解，消化）及其与渗透的相互作用，以更好地了解配制为ADDS的非洛地平的吸收。实验在μFLUX仪器中进行,由两个房间组成，代表肠和浆膜室，由Caco-2单层隔开。在溶解-消化-渗透实验期间，将ADDS添加到含有模拟肠液和固定化脂肪酶的供体区室中。使用原位UV探针或监测两个隔室中的溶解和渗透，当浊度干扰测量时，用HPLC分析。该方法表明，与使用结晶非洛地平的条件相比，所有ADDS都增加了供体和受体浓度。隔室之间的相关性差表明需要浆膜隔室来评估来自ADDS的药物吸收。该方法可以进行中等通量评估：（i）小肠中发生的动态过程，和(ii)实时药物浓度。
