Klitgaard Mette, Beilles Stephane, Sassene Philip Jonas, Berthelsen Ragna, Müllertz Anette
Department of Pharmacy, University of Copenhagen, Copenhagen 2100, Denmark.
Pharmaceutical Science Department, Sanofi, Montpellier 34080, France.
Mol Pharm. 2020 Sep 8;17(9):3214-3222. doi: 10.1021/acs.molpharmaceut.0c00307. Epub 2020 Aug 5.
Drug release from a lipid-based drug delivery system (LbDDS) is typically studied using a one-step intestinal digestion model. However, lately the importance of incorporating gastric digestion has been stressed. The aim of the present study was to compare a two-step gastro-intestinal (GI) digestion model to the commonly used one-step intestinal digestion model. The models were evaluated by studying release of the model drug A1260 from two LbDDSs (F-I and F-II), for which pharmacokinetic data from oral administration to beagle dogs were available. The amount of A1260 recovered in the aqueous phases during and after the GI digestion of F-I and F-II was related to the and AUC of the plasma concentration-time profiles of each formulation and produced a rank order - (IVIV) relation. In comparison, a similar IVIV rank ordering was obtained when relating the amount of A1260 recovered in the aqueous phase prior ( = 0 min), and following 15 min of intestinal digestion, to the plasma concentration-time profiles. However, after 60 min of intestinal digestion, the LbDDSs performed equally in the one-step digestion model, contrary to what was observed in the two-step digestion model, and . As the GI digestion model produced a clearer distinction in terms of LbDDS rank ordering of the two LbDDSs, compared to the intestinal digestion model, it was found to be a promising model to study and estimate the LbDDS behavior .
基于脂质的药物递送系统（LbDDS）的药物释放通常采用一步肠道消化模型进行研究。然而，最近已强调了纳入胃消化的重要性。本研究的目的是将两步胃肠道（GI）消化模型与常用的一步肠道消化模型进行比较。通过研究模型药物A1260从两种LbDDS（F-I和F-II）中的释放来评估这些模型，对于这两种LbDDS，有从口服给予比格犬获得的药代动力学数据。在F-I和F-II的GI消化期间及之后水相中回收的A1260量与每种制剂的血浆浓度-时间曲线的 和AUC相关，并产生了等级顺序 - （体内-体外）关系。相比之下，当将在水相中在之前（ = 0分钟）以及在肠道消化15分钟后回收的A1260量与血浆浓度-时间曲线相关联时，获得了类似的体内-体外等级排序。然而，在肠道消化60分钟后，LbDDS在一步消化模型中的表现相同，这与在两步消化模型中观察到的情况相反，以及 。由于与肠道消化模型相比，GI消化模型在两种LbDDS的LbDDS等级排序方面产生了更明显的区别，因此发现它是研究和估计LbDDS行为的一个有前景的模型。
