Food Effects & the Fed Gastric Medium
The gastrointestinal juices in the stomach, small intestine and colon are highly complex and variable. A large factor in their variability is the prandial state (i.e. fed and fasted). In the early months of 2019 we will be releasing fed gastric medium, the final step in offering complete coverage of the three main sections of the gastrointestinal tract, in both prandial states. This will allow users to test for potential food effects on their drug products as they move through the gastrointestinal tract.
After a meal, the quantities of bile fluids and lipids are much higher, the pH of the stomach increases, and gastric emptying time is slower. This massively influences the rate of dissolution and absorption of a drug and is known as a food effect.
Food effects on the dissolution of drugs take three main forms; pH changes, increased levels of bile fluids, and physiological changes, as explained below.
In the fasted state the pH of the stomach is around 2, and immediately after a meal it rises to roughly 5/6. In contrast, the intestine has a pH of approximately 6.5 in the fasted state, and after food it decreases to roughly 6. These are all approximate values however, and are subject to high variability, which is precisely why it is important to investigate the resulting effects. Such pH changes are important when the drug product is an acid or a base, as its solubility is pH dependent. For example, ibuprofen is acidic (pKa = 4.9), and so we would expect that it has a lower solubility in the fasted stomach compared to the fed, and vice versa in the intestine.
Secondly, an important factor in the dissolution of a compound is its solubility in water compared to lipids. The comparison of these two solubilities can be quantified with the ‘LogP’ value which is a partition coefficient that measures lipophilicity. After eating, the levels of lipids and bile fluids in the gastrointestinal juices sharply increases, which means that highly lipophilic/hydrophobic drugs will become more soluble in the fed state.
Finally, eating food induces physiological effects on the gastrointestinal tract, an example of which is slowed gastric emptying and intestinal transit. This means that when taken with food, a drug is likely to take longer to reach the site of absorption (small intestine), and therefore have a delayed Tmax (time at which max. plasma concentration is reached).
By considering the ranging effects that food can have on the dissolution and solubility of a drug, it is clear why it is essential to test for them during formulation. With the introduction of fed gastric medium in 2019, biorelevant users will be able to quantitatively test for food effects in vitro, for all three main gastrointestinal sections. This allows a much clearer insight into how food effects will influence their drug in vivo, as it passes through the gastrointestinal tract.
If you would like to be notified when it is launched, please register your interest through our contact form.