کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2481723 1556246 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Prediction of food effect by bile micelles on oral drug absorption considering free fraction in intestinal fluid
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Prediction of food effect by bile micelles on oral drug absorption considering free fraction in intestinal fluid
چکیده انگلیسی

The purpose of the present study was to derive a theoretical framework for prediction of the food effects by interactions with bile micelles on oral drug absorption. The effect of bile micelles was discussed based on the categories of permeability limited (PL), dissolution rate limited (DRL) and solubility limited (SL) absorption. SL was further categorized as the solubility–epithelial membrane limited (SL-E) and the solubility–unstirred water layer (UWL) limited (SL-U). In PL, an increase of bile micelles in the fed state was suggested to result in a negative food effect if the drug molecules bind to bile micelles because of a decrease of free monomer concentration. In DRL, a positive food effect was anticipated. In SL-E (e.g., pranlukast), little or no food effect was anticipated since the increase of apparent solubility (bile micelle bound molecule + free molecule) would be cancelled out by the decrease of effective permeability (the free monomer concentration at the epithelial membrane surface would remain the same. Total flux = solubility × permeability). In SL-U (e.g., danazol), a positive food effect was anticipated since the bile micelle bound molecules can permeate the UWL (however, slower than free monomer molecules). Based on this discussion, it was suggested that a formulation which could increase the free fraction at the epithelial membrane surface would be required to enhance oral absorption for SL-E (e.g., supersaturable formulations), whereas any formulation which can increase the UWL flux would be effective for SL-U (e.g., micro- to nano-emulsion systems, nano-milling and cyclodextrins). It was also suggested that a simple dissolution test would be misleading for SL-E and a simultaneous assessment of dissolution and permeation would be required.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutical Sciences - Volume 40, Issue 2, 12 May 2010, Pages 118–124
نویسندگان
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