Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano
{"title":"碳酸氢盐缓冲液对药物人工膜渗透的影响。","authors":"Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano","doi":"10.5599/admet.2603","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and purpose: </strong>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.</p><p><strong>Experimental approach: </strong>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 (<i>β</i>)= 4.4 mM pH<sup>-1</sup>). Phosphate buffer (PPB) with the same pH and <i>β</i> was used for comparison (PPB = 8 mM).</p><p><strong>Key results: </strong>The floating lid suppressed the pH increase to less than 0.1 for 120 min. The effective permeability (<i>P</i> <sub>e</sub>) values of lipophilic weakly acidic and basic drugs were lower in BCB than in PPB (ketoprofen, naproxen, and propranolol). On the other hand, the <i>P</i> <sub>e</sub> values in BCB and PPB were similar for unionizable drugs (caffeine and antipyrine) and hydrophilic weakly basic drugs (metoprolol and procainamide).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 1","pages":"2603"},"PeriodicalIF":3.4000,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954139/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effect of bicarbonate buffer on artificial membrane permeation of drugs.\",\"authors\":\"Shiori Ishida, Samuel Lee, Balint Sinko, Karl Box, Kiyohiko Sugano\",\"doi\":\"10.5599/admet.2603\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and purpose: </strong>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.</p><p><strong>Experimental approach: </strong>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 (<i>β</i>)= 4.4 mM pH<sup>-1</sup>). Phosphate buffer (PPB) with the same pH and <i>β</i> was used for comparison (PPB = 8 mM).</p><p><strong>Key results: </strong>The floating lid suppressed the pH increase to less than 0.1 for 120 min. The effective permeability (<i>P</i> <sub>e</sub>) values of lipophilic weakly acidic and basic drugs were lower in BCB than in PPB (ketoprofen, naproxen, and propranolol). On the other hand, the <i>P</i> <sub>e</sub> values in BCB and PPB were similar for unionizable drugs (caffeine and antipyrine) and hydrophilic weakly basic drugs (metoprolol and procainamide).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":7259,\"journal\":{\"name\":\"ADMET and DMPK\",\"volume\":\"13 1\",\"pages\":\"2603\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954139/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ADMET and DMPK\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5599/admet.2603\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ADMET and DMPK","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5599/admet.2603","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Effect of bicarbonate buffer on artificial membrane permeation of drugs.
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 (Pe) values of lipophilic weakly acidic and basic drugs were lower in BCB than in PPB (ketoprofen, naproxen, and propranolol). On the other hand, the Pe 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.
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
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