弥合体外与体内溶解度-渗透性相互作用之间的差距。

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Michinori Oikawa, Satoru Matsuura, Takeyuki Okudaira, Ryo Ito, Kanako Arima, Masahiro Fushimi, Takamasa Oda, Kaoru Ohyama, Kohsaku Kawakami
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引用次数: 0

摘要

溶解性差的药物使用增溶载体可能会降低药物分子的活性,从而干扰跨膜吸收,这就是所谓的溶解度-渗透性相互作用。然而,尽管许多体外研究表明使用增溶载体会对口服吸收产生负面影响,但能显示这种相互作用效应的体内研究却很有限。本研究以地塞米松为模型药物,对环糊精的相互作用效应进行了系统的体外、原位和体内研究。评估方法包括通过聚合物膜、人工脂质膜、细胞膜和肠道闭环膜的渗透。然后,将结果与小鼠和狗的口服研究进行比较。虽然在体外研究中明显观察到了相互作用效应,但在体内研究中却没有发现明显的相互作用,这表明相互作用效应在体外渗透研究中更为突出。体内无相互作用的原因包括胃肠道的稀释效应、药物与活体成分的相互作用以及药物在膜渗透后的清除。总之,这项研究清楚地表明了体外渗透研究在预测增溶剂口服后的相互作用效应方面的适用性和局限性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bridging the gap between in vitro and in vivo solubility-permeability interplay.

Use of solubilization carriers for poorly soluble drugs may disturb transmembrane absorption by lowering the activity of drug molecules, which is known as the solubility-permeability interplay. However, although many in vitro studies have indicated the negative impacts of use of solubilization carriers for oral absorption, in vivo studies that showed the interplay effect are limited. This study provides systematic in vitro, in situ, and in vivo investigation of the interplay effect of cyclodextrin using dexamethasone as a model drug. The evaluation methods included permeation through polymeric, artificial lipid, cell, and intestinal closed-loop membranes. Then, the results were compared with oral administration studies in mice and dogs. Although the interplay effect was clearly observed in the in vitro studies, no obvious interplay was found in the in vivo studies, suggesting that the interplay effect is more prominent in the in vitro permeation studies. Absence of in vivo interplay was attributed to the dilution effect in the gastrointestinal tract, interaction of the drug with living components, and clearance of the drug after membrane permeation. Overall, this investigation clearly demonstrated the applicability and limitations of in vitro permeation studies for predicting the interplay effects of solubilizers after the oral administration.

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来源期刊
CiteScore
7.30
自引率
13.20%
发文量
367
审稿时长
33 days
期刊介绍: The Journal of Pharmaceutical Sciences will publish original research papers, original research notes, invited topical reviews (including Minireviews), and editorial commentary and news. The area of focus shall be concepts in basic pharmaceutical science and such topics as chemical processing of pharmaceuticals, including crystallization, lyophilization, chemical stability of drugs, pharmacokinetics, biopharmaceutics, pharmacodynamics, pro-drug developments, metabolic disposition of bioactive agents, dosage form design, protein-peptide chemistry and biotechnology specifically as these relate to pharmaceutical technology, and targeted drug delivery.
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