Klitgaard Mette, Müllertz Anette, Berthelsen Ragna
Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
Bioneer: FARMA, Department of Pharmacy, University of Copenhagen, 2100 Copenhagen, Denmark.
Pharmaceutics. 2021 Apr 2;13(4):489. doi: 10.3390/pharmaceutics13040489.
The aim of this study was to design an in vitro lipolysis-permeation method to estimate drug absorption following the oral administration of self-nanoemulsifying drug delivery systems (SNEDDSs). The method was evaluated by testing five oral formulations containing cinnarizine (four SNEDDSs and one aqueous suspension) from a previously published pharmacokinetic study in rats. In that study, the pharmacokinetic profiles of the five formulations did not correlate with the drug solubilization profiles obtained during in vitro intestinal lipolysis. Using the designed lipolysis-permeation method, in vitro lipolysis of the five formulations was followed by in vitro drug permeation in Franz diffusion cells equipped with PermeaPad barriers. A linear in vivo-in vitro correlation was obtained when comparing the area under the in vitro drug permeation-time curve (AUC), to the AUC of the plasma concentration-time profile obtained from the in vivo study. Based on these results, the evaluated lipolysis-permeation method was found to be a promising tool for estimating the in vivo performance of SNEDDSs, but more studies are needed to evaluate the method further.
本研究的目的是设计一种体外脂解-渗透方法，以评估口服自纳米乳化药物递送系统（SNEDDSs）后的药物吸收情况。通过测试五种含桂利嗪的口服制剂（四种SNEDDSs和一种水悬浮液）对该方法进行评估，这些制剂来自之前发表的大鼠药代动力学研究。在该研究中，五种制剂的药代动力学曲线与体外肠道脂解过程中获得的药物溶解曲线不相关。使用所设计的脂解-渗透方法，对五种制剂进行体外脂解，然后在配备PermeaPad屏障的Franz扩散池中进行体外药物渗透。将体外药物渗透-时间曲线下面积（AUC）与体内研究获得的血浆浓度-时间曲线的AUC进行比较时，获得了线性体内-体外相关性。基于这些结果，发现所评估的脂解-渗透方法是评估SNEDDSs体内性能的一种有前景的工具，但需要更多研究来进一步评估该方法。
