Ishida Shiori, Lee Samuel, Sinko Balint, Box Karl, Sugano Kiyohiko
Molecular Pharmaceutics Lab., College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1, Noji-higashi, Kusatsu, Shiga 525-8577, Japan.
Pion Inc. (UK) Ltd. Forest Row Business Park, Station Road, East Sussex, RH18 5DW, United Kingdom.
ADMET DMPK. 2025 Jan 18;13(1):2603. doi: 10.5599/admet.2603. eCollection 2025.
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.
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 ()= 4.4 mM pH). Phosphate buffer (PPB) with the same pH and was used for comparison (PPB = 8 mM).
The floating lid suppressed the pH increase to less than 0.1 for 120 min. The effective permeability ( ) values of lipophilic weakly acidic and basic drugs were lower in BCB than in PPB (ketoprofen, naproxen, and propranolol). On the other hand, the values in BCB and PPB were similar for unionizable drugs (caffeine and antipyrine) and hydrophilic weakly basic drugs (metoprolol and procainamide).
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.
小肠的pH值通过碳酸氢盐缓冲液（BCB）在生理状态下维持。然而，BCB对药物膜渗透的影响尚未得到研究。本研究的目的是探究BCB对药物被动膜渗透的影响。
使用μFlux仪器（pION公司）进行渗透性测量。为避免BCB的pH值变化，新开发了一种用于μFlux的浮动盖。膜过滤器用10%大豆卵磷脂-癸烷溶液包被。通量测量在等pH条件下进行（pH 6.5，BCB = 10 mM，缓冲容量（）= 4.4 mM pH）。使用具有相同pH和的磷酸盐缓冲液（PPB）进行比较（PPB = 8 mM）。
浮动盖在120分钟内将pH值升高抑制至小于0.1。亲脂性弱酸和弱碱性药物在BCB中的有效渗透率（）值低于在PPB中的值（酮洛芬、萘普生和普萘洛尔）。另一方面，对于非离子化药物（咖啡因和安替比林）和亲水性弱碱性药物（美托洛尔和普鲁卡因胺），BCB和PPB中的值相似。
亲脂性弱酸和弱碱性药物在BCB中的被动膜渗透比在PPB中慢。这被认为归因于BCB的缓慢中和速率，其影响膜表面附近的pH值。
