Effect of Ingested Lipids on Drug Dissolution and Release with Concurrent Digestion: A Modeling Approach
Effect of Ingested Lipids on Drug Dissolution and Release with Concurrent Digestion: A Modeling Approach
复制标题
DOI：
10.1007/s11095-013-1238-6
复制
发表时间：
2013-12-01
影响因子：
3.7
通讯作者：
Carrier, Rebecca L.
中科院分区：
文献类型：
--
作者：
Buyukozturk, Fulden;Di Maio, Selena;Carrier, Rebecca L.
从机制上研究和建模来自食物或自乳化药物递送系统（SEDDS）的脂质对肠腔中药物转运的影响。针对两种给药方案进行了同时脂质消化、溶解/释放和药物分配的实验研究和建模：固体药物与食物相关的脂质在一个实施方案中，将药物溶解在模型SEDDS（大豆油和吐温80，1：1的比例）中。消化速率常数，乳液液滴的渗透性，在胶束和油相的分配系数进行了测量，并用于数值求解所开发的model.Strong影响的脂肪消化药物从SEDDS和固体药物溶出到食品相关的脂肪乳剂的药物释放观察和预测的模型。在引入SEDDS后90分钟，在不存在和存在消化的情况下分别有9%和70%的药物释放。然而，在食物相关脂质存在下，药物的整体溶出时间比不消化时长，基于系统的机制模型结合了药物与脂质同时给药的动态过程，能够预测水溶液中药物的浓度分布。该模型一旦与考虑脂质存在下药物吸收和药物淋巴转运过程的药代动力学模型相结合，对于定量预测脂质对药物生物利用度的影响可能非常有用。
To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen.Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model.Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion was observed and predicted by the developed model. Ninety minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion.A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs.