Dahlgren David, Sjögren Erik, Lennernäs Hans
Department of Pharmaceutical Biosciences, Translational Drug Discovery and Development, Uppsala University, Sweden.
ADMET DMPK. 2020 Sep 17;8(4):375-390. doi: 10.5599/admet.881. eCollection 2020.
An established pharmaceutical strategy to increase oral drug absorption of low solubility-high permeability drugs is to create nanoparticles of them. Reducing the size of the solid-state particles increases their dissolution and transport rate across the mucus barrier and the aqueous boundary layer. Suspensions of nanoparticles also sometimes behave differently than those of larger particles in the fed state. This review compares the absorption mechanisms of nano- and larger particles in the lumen at different prandial states, with an emphasis on data derived from in vivo models. Four BSC class II drugs-aprepitant, cyclosporine, danazol and fenofibrate-are discussed in detail based on information from preclinical intestinal perfusion models.
一种已确立的提高低溶解度-高渗透性药物口服吸收的制药策略是制备它们的纳米颗粒。减小固态颗粒的尺寸可提高其溶解速率以及跨黏液屏障和水相边界层的转运速率。纳米颗粒混悬液在进食状态下的行为有时也与较大颗粒的混悬液不同。本综述比较了不同用餐状态下纳米颗粒和较大颗粒在肠腔中的吸收机制,重点是来自体内模型的数据。基于临床前肠道灌注模型的信息,详细讨论了四种生物药剂分类系统(BSC)II类药物——阿瑞匹坦、环孢素、达那唑和非诺贝特。