目的:测试并排扩散模型是否适合研究吸收环境中的药物过饱和。
方法:µD/P模型和µFLUX模型,使用Caco-2细胞单层/PAMPA膜作为渗透屏障,分别,在鲁棒性和易操作性方面进行了比较,同时研究药物的过饱和-沉淀-渗透相互作用。继续使用最好的模型,受体介质的影响以及在组合的溶解-渗透模型中研究药物过饱和的重要性,与简单的溶解模型相比,进行了评估。
结果:两个模型在过饱和度方面产生了相似的结果,沉淀和渗透。μFLUX模型基于其无细胞渗透系统被认为更稳健且更易于处理。使用μFLUX模型,发现具有高表面活性剂浓度的受体介质增加了渗透药物的量。发现吸收对药物过饱和的影响取决于药物,和过饱和的测试水平。
结论:测试的模型具有可比性;然而,Caco-2细胞单层被认为太敏感而不能用于研究药物过饱和。需要进一步的研究来评估观察到的药物吸收对药物过饱和的依赖作用。
OBJECTIVE: To test whether a side-by-side diffusion model is suitable for studying drug supersaturation in an absorptive environment.
METHODS: The µD/P model and the µFLUX model, using a Caco-2 cell monolayer/PAMPA membrane as the
permeation barrier, respectively, were compared in terms of robustness and ease of handling, while studying the drug supersaturation-precipitation-
permeation interplay. Continuing with the best model, the impact of the acceptor media and the importance of studying drug supersaturation in a combined dissolution-
permeation model, as compared to a simple dissolution model, were evaluated.
RESULTS: The two models produced similar results in terms of supersaturation, precipitation and
permeation. The µFLUX model was considered more robust and easier to handle based on its cell-free
permeation system. Using the µFLUX model, it was found that an acceptor medium with a high surfactant concentration increased the amount of permeated drug. The effect of absorption on drug supersaturation was found to be dependent on the drug, and the tested level of supersaturation.
CONCLUSIONS: The tested models were comparable; however, Caco-2 cell monolayers were considered too sensitive to be used to study drug supersaturation. Further studies are needed to evaluate the observed drug-dependent effects of absorption on drug supersaturation.