Effect of bicarbonate buffer on artificial membrane permeation of drugs.

IF 3.4 Q2 CHEMISTRY, MEDICINAL

ADMET and DMPK Pub Date : 2025-01-18 eCollection Date: 2025-01-01 DOI:10.5599/admet.2603

Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano

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引用次数: 0

Abstract

Background and purpose: The pH value of the small intestine is physiologically maintained by bicarbonate buffer (BCB). However, the effect of BCB on the membrane permeation of drugs has not been investigated. The purpose of this study was to investigate the effect of BCB on the passive membrane permeation of drugs.

Experimental approach: The μFlux apparatus (pION Inc.) was used for permeability measurements. To avoid a pH change of BCB, a floating lid was newly developed for μFlux. The membrane filter was coated with a 10 % soybean lecithin-decane solution. The flux measurement was performed in an iso-pH condition (pH 6.5, BCB = 10 mM, buffer capacity (β)= 4.4 mM pH^-1). Phosphate buffer (PPB) with the same pH and β was used for comparison (PPB = 8 mM).

Key results: The floating lid suppressed the pH increase to less than 0.1 for 120 min. The effective permeability (P _e) values of lipophilic weakly acidic and basic drugs were lower in BCB than in PPB (ketoprofen, naproxen, and propranolol). On the other hand, the P _e values in BCB and PPB were similar for unionizable drugs (caffeine and antipyrine) and hydrophilic weakly basic drugs (metoprolol and procainamide).

Conclusion: Passive membrane permeation of lipophilic weakly acidic and basic drugs was slower in BCB than in PPB. This was suggested to be attributed to the slow neutralization rate of BCB, which affects the pH value adjacent to the membrane surface.

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碳酸氢盐缓冲液对药物人工膜渗透的影响。

背景与目的：碳酸氢盐缓冲液（BCB）在生理上维持小肠的pH值。然而，bbcb对药物膜透性的影响尚未被研究。本研究旨在探讨BCB对药物被动膜渗透的影响。实验方法：采用μFlux仪（pION Inc.）测量磁导率。为了避免BCB的pH变化，我们设计了一种浮盖来装μFlux。膜过滤器涂有10%的大豆卵磷脂-癸烷溶液。通量测量在等pH条件下进行（pH 6.5, BCB = 10 mM，缓冲容量(β)= 4.4 mM pH-1）。采用pH和β相同的磷酸盐缓冲液（PPB = 8 mM）进行比较。关键结果：浮盖抑制pH升高至小于0.1，持续120min。亲脂性弱酸性和碱性药物（酮洛芬、萘普生、心得安）在BCB中的有效渗透率（P e）值低于PPB。另一方面，可联合药物（咖啡因和安替比林）和亲水弱碱性药物（美托洛尔和普鲁卡因胺）在BCB和PPB中的P值相似。结论：亲脂性弱酸性和碱性药物在BCB中被动膜渗透较PPB慢。这可能是由于BCB的中和速率较慢，影响了膜表面附近的pH值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ADMET and DMPK Multiple-

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

4 weeks

期刊介绍： ADMET and DMPK is an open access journal devoted to the rapid dissemination of new and original scientific results in all areas of absorption, distribution, metabolism, excretion, toxicology and pharmacokinetics of drugs. ADMET and DMPK publishes the following types of contributions: - Original research papers - Feature articles - Review articles - Short communications and Notes - Letters to Editors - Book reviews The scope of the Journal involves, but is not limited to, the following areas: - physico-chemical properties of drugs and methods of their determination - drug permeabilities - drug absorption - drug-drug, drug-protein, drug-membrane and drug-DNA interactions - chemical stability and degradations of drugs - instrumental methods in ADMET - drug metablic processes - routes of administration and excretion of drug - pharmacokinetic/pharmacodynamic study - quantitative structure activity/property relationship - ADME/PK modelling - Toxicology screening - Transporter identification and study