In vitro models for the determination of drug absorption and a prediction of dissolution/absorption relationships

Abstract

Drugs contained in a solid pharmaceutical form should be adequately water soluble and permeable, into the intestine in order to be effectively absorbed after oral administration. The speed and extent at which a drug is absorbed can vary due to its physicochemical characteristics and factors related to disintegration and dissolution of the drug. According to Biopharmaceutical Drug System Classification (BSC), the dissolution and the intestinal permeation of a drug can limit the absorption and, consequently, the therapeutic action of that drug. This article focuses on data concerning the predictability of dissolution and absorption of drugs using in vitro models. There are several methods for determining in vitro intestinal permeability. These include diffusion studies with intestinal segments from various species or with cultured cell monolayer. Some of the most commonly used cell models are Caco-2, TC-7, 2/4/A1 and MDCK. Caco-2 cells have been the most extensively characterized and useful cell models. The Caco-2 cell, a human colon adenocarcinoma, undergoes spontaneous enterocytic differentiation in culture. A dissolution Caco-2 system has been developed to predict dissolution/absorption relationships of oral solid dosage forms of drugs prior to human studies. The in vitro permeability models represent an important tool for drug discovery within the pharmaceutical industry. However, similar models are likely to generate false negative results with actively transported drugs, and the use of a sophisticated mathematical model could be required.