期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 108, 期 9, 页码 2917-2925出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2019.04.006
关键词
nanoparticle(s); amorphous solid dispersion(s) (ASD); bioavailability; absorption, pharmacokinetics, solid dispersion(s)
Amorphous solid dispersions (ASDs) are used as bioavailability-enhancing formulations on the premise of the increased solubility of the amorphous form over its crystalline counterpart. Recent studies have shown that ASDs can, during dissolution, generate amorphous nanoparticles that were initially postulated to serve as a source of rapidly dissolving compound during absorption. Researchers have proposed that nanoparticles, including crystalline nanoparticles, may provide additional benefits to absorption such as drifting in the mucous layer. However, there are limited published data on the impact of nanoparticle size on bioavailability in vivo and, to our knowledge, there have been no published examples looking at the impact of differential size of in situegenerated nanoparticles from an ASD. Anacetrapib, a highly lipophilic, Biopharmaceutics Classification System IV compound, formulated as an ASD that generates nanoparticles on dissolution, was used in the studies described in this article. A differential response in bioavailability was observed with similar to 100 nm or smaller particles, resulting in higher average exposure compared to similar to 200 nm or larger particles. This increase in bioavailability could not be fully accounted for by the improvement in dissolution rate and was not as pronounced as that achieved by improving solubilization by coadministration with a high-fat meal. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据