Felicijan Tjaša, Rakoše Iva, Prislan Manca, Locatelli Igor, Bogataj Marija, Trontelj Jurij
Department of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia.
Pharmaceutics. 2024 Aug 3;16(8):1040. doi: 10.3390/pharmaceutics16081040.
Food can change various physiological parameters along the gastrointestinal tract, potentially impacting postprandial drug absorption. It is thus important to consider different in vivo conditions during in vitro studies. Therefore, a novel dissolution medium simulating variable postprandial pH values and lipid concentrations was developed and used in this study. Additionally, by establishing and validating a suitable analytical method, the effects of these parameters on the dissolution of a model drug, cinnarizine, and on its distribution between the lipid and aqueous phases of the medium were studied. Both parameters, pH value and lipid concentration, were shown to influence cinnarizine behavior in the in vitro dissolution studies. The amount of dissolved drug decreased with increasing pH due to cinnarizine's decreasing solubility. At pH values 5 and 7, the higher concentration of lipids in the medium increased drug dissolution, and most of the dissolved drug was distributed in the lipid phase. In all media with a lower pH of 3, dissolution was fast and complete, with a significant amount of drug distributed in the lipid phase. These results are in accordance with the in vivo observed positive food effect on cinnarizine bioavailability described in the literature. The developed medium, with its ability to easily adjust the pH level and lipid concentration, thus offers a promising tool for assessing the effect of co-ingested food on the dissolution kinetics of poorly soluble drugs.
食物可改变胃肠道的各种生理参数，可能影响餐后药物吸收。因此，在体外研究期间考虑不同的体内条件很重要。因此，本研究开发并使用了一种模拟餐后不同pH值和脂质浓度的新型溶出介质。此外，通过建立和验证合适的分析方法，研究了这些参数对模型药物桂利嗪溶出及其在介质脂质相和水相之间分布的影响。在体外溶出研究中，pH值和脂质浓度这两个参数均显示会影响桂利嗪的行为。由于桂利嗪溶解度降低，药物溶出量随pH值升高而减少。在pH值为5和7时，介质中较高的脂质浓度增加了药物溶出，且大部分溶解药物分布在脂质相中。在所有pH值较低的3的介质中，溶出快速且完全，大量药物分布在脂质相中。这些结果与文献中描述的体内观察到的食物对桂利嗪生物利用度的积极影响一致。所开发的介质能够轻松调节pH水平和脂质浓度，因此为评估同时摄入的食物对难溶性药物溶出动力学的影响提供了一种有前景的工具。
