Intestinal tract simulation

In addition to the potential of liberating the active drug upon absorption, orally applicable prodrugs require a sufficient stability in the gastro-intestinal tract which is most importantly pH-dependant chemical stability. This can be studied with simulated gastrointestinal fluids (Balbach and Korn 2004). Also... 

A further series of experiments assessed the stability of the conjugates to the two major sets of digestive enzymes commonly present in the human digestive tract simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). For each of the incubations, the rate of degradation of the conjugate was measured over 24 hours by LC-MS/MS. 

Aeromonades are frequent inhabitants of the intestinal tract of coldblooded animals and are almost always to be found in surface waters and in waste water. These bacteria are to be found relatively rarely in the intestinal contents of human beings and warm-blooded animals. Some representatives of the aeromonas genus can also cause lactose to ferment at 37 C and can, in certain circumstances, simulate the presence of coliform bacteria. 

The second situation when IVIVC is not likely for class II drugs is where the absorption is limited by the saturation solubility in the gastrointestinal tract rather than the dissolution rate, as discussed in more detail above. In this situation, the drug concentration in the gastrointestinal tract will be close to the saturation solubility, and changes of the dissolution rate will not affect the plasma concentrationtime profile and in vivo bioavailability. Standard in vitro dissolution tests are carried out under sink conditions , i.e., at concentrations well below the saturation solubility. Thus, only effects related to dissolution rate can be predicted in vitro. If more physiologically relevant dissolution media are used, which do not necessarily provide sink conditions , the possibility for IVIVC could be improved, as has been indicated by the results of recent studies using simulated intestinal medium [76],... 

The small-intestinal transit flow is a fundamental process for all gastrointestinal absorption phenomena. However, the structure of the gastrointestinal tract is highly complex and it is practically impossible to explicitly write and solve the equations of motion for the drug flow. Instead, numerical computer simulation techniques that incorporate the heterogeneous features of the gastrointestinal wall structure and of the drug flow are used in this section to characterize the intestinal transit process in humans. 

Flow calorimetry has also been used to investigate dosage forms. Dissolution of tablets under various simulated conditions has been explored, for example. Here, the tablet is presented with various solutions designed to mimic conditions in the gastro intestinal (GI) tract (pH 7 buffer) and stomach (pH 3 buffer for fasting and lipid solutions for fatty meals). The rate of dissolution can then be estimated for conditions in vivo. 

Weak bases have higher solubility at low pH values, and a combination of media simulating the fasted gastric fluids and media simulating the fasted intestinal fluids will be suitable to simulate their dissolution behaviour in the GI tract. The model used should be able to simulate possible precipitation of a weak base when transferred from an acidic to a neutral medium. In the fed... 

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