Materials and Microenvironments for Engineering the Intestinal Epithelium.

The barrier functions of the gastrointestinal tract rely in large part on a single layer of columnar intestinal epithelial cells. These epithelial cells are mediators of intestinal homeostasis, regulating and communicating biochemical signals between underlying stromal cells and luminal cues. The development of representative in vitro models to recapitulate the gastrointestinal epithelium is crucial to understanding cell-cell interactions during intestinal homeostasis and dysfunction.

Predicting the effect of fed-state intestinal contents on drug dissolution.

Purpose: There are several endogenous and exogenous species in the gastrointestinal (GI) tract which can act as solubilizing agents and thereby affect drug dissolution. The purpose of this study is to understand food effects on drug dissolution and provide insight into their anticipated overall effect on absorption and bioavailability.

Methods: Dissolution kinetics of 15 drugs of variable logP, charge, and molecular weight were tested in simulated intestinal environment.

Drug salts and solubilization: modeling the influence of cyclodextrins on oral absorption.

Substantial effort and resources are spent for the oral delivery of low solubility compounds using drug delivery technologies. Complexation using cyclodextrins (CDs) is one popular strategy used to enhance drug dissolution kinetics and solubility. In addition to delivery technologies, another common method of improving dissolution kinetics of a low solubility compound is to dose it as a salt.

Modeling the influence of cyclodextrins on oral absorption of low solubility drugs: II. Experimental validation.

A model was developed for predicting the influence of cyclodextrins (CDs) delivered as a physical mixture with drug on oral absorption. CDs are cyclic oligosaccharides which form inclusion complexes with many drugs and are often used as solubilizing agents. The purpose of this work is to compare the simulation predictions with in vitro as well as in vivo experimental results to test the model's ability to capture the influence of CD on key processes in the gastrointestinal (GI) tract environment.

Modeling the influence of cyclodextrins on oral absorption of low-solubility drugs: I. Model development.

The ability to quantitatively predict the influence of a solubilization technology on oral absorption would be highly beneficial in rational selection of drug delivery technology and formulation design. Cyclodextrins (CDs) are cyclic oligosaccharides which form inclusion complexes with a large variety of compounds including drugs. There are many studies in the literature showing that complexation between CD and drug enhances oral bioavailability and some demonstrating failure of CD in bioavailability enhancement, but relatively little guidance regarding when CD can be used to enhance bioavailability.