Drug Absorbed Administration

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Introduction

The oral route is still the most desired route for the administration of medicinal products1 due to the ease and lack of inconvenience associated with this administration route, in comparison to others such as the pulmonary route or the more invasive intravenous route. The pharmaceutical industry has developed considerably over the past 40 years with respect to the rate at which new chemical entities are being discovered. This increased rate is primarily due to the invention of high throughput screening, but there is no correlation between the rate of synthesis of these novel compounds and the release of new drugs on the market due to the high failure rate during the development process1. In order to minimise cost and resources associated with this loss, effective screening methods for both pharmacological action and bioavailability have to be used. The most important process that influences bioavailability of the drug is absorption and the necessity of creating and using suitable models that can predict the in vivo absorption profile of a drug is absolutely critical in achieving the desired reduction in cost associated with the pharmaceutical development process. There are two primary phases of absorption for orally administered drugs; the first is dissolution of the drug in the aqueous media present at the site or sites of absorption1 the second is permeation of the drug particles in solution through predominantly the small intestinal membrane into the hepatic portal vein1. The main factors affecting dissolution of a drug in the gastrointestinal (GI) system are the pH of the environment, volume of dissolution media and the presence of food by either encouraging or delaying the passage of the dosage form into the small intestine where many drugs are absorbed. Permutation of the drug through the small intestinal membrane is influenced by several variables. The presence of influx and efflux pumps on the apical surface is a main consideration2. There are three main routes of absorption that drugs can take; transcellular absorption through the cells, paracellular absorption by passing thorough the tight junctions between cells or by using influx transporters present on the apical surface3. Efflux transporters are also present which act to eject the drug molecule out of the cell and limit bioavailability1. All of these processes and scenarios need to be considered in developing an in vitro model to accurately predict gastrointestinal drug absorption. The extent to which a particular model represents the results seen in vivo can be conveyed through a mathematical relationship known as the in vitro- in vivo correlation (IVIVC)2,4. The predictive power of this correlation ultimately depends upon the capacity of the in vitro method used to simulate and reflect what occurred in vivo. The fact that different models are able to do this to different degrees has been appreciated as different levels of IVIVC have been defined; levels A, B, C, multiple C and D with A being the highest level5. There are many factors to consider and appreciate when looking at IVIVC made from drugs absorbed from the gastrointestinal tract,

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