Gastrointestinal Fluids and Biorelevant Media

A drug encounters various types of gastrointestinal fluids as it journeys through the gut. These in vivo fluids have distinct properties so the drug will often have very different dissolution profiles in them. Furthermore, eating a meal changes the properties of gastrointestinal fluids dramatically. This in turn can affect the way the drug dissolves and is subsequently absorbed by the body.

In the context of immediate release oral drugs, this entry summarizes the most important fluids in the upper gastrointestinal tract before a meal (fasted state) and after a meal (fed state) and how they can be simulated.

1.           Fasted stomach fluid

After swallowing the dosage form with a glass of water, the first important fluid that the drug encounters is fasted stomach fluid. This is comprised of the liquid swallowed with the drug and the acidic gastric fluid already present in the fasting stomach. In healthy humans, fasted gastric fluid has a comparatively acidic pH compared to other sections of the fasted gut. This low gastric pH offers protection against undesirable microbes entering the upper gastrointestinal tract by creating a more hostile environment. Fasted gastric fluid also contains low levels of surfactants refluxed back into the stomach from the top section of the small intestine as the stomach pylorus (gate) opens.

Fasted gastric fluid is kept briefly in the stomach before being emptied into the small intestine. The stomach functions as a kind of reservoir and is not intended for absorption so its fluid does not play a significant role in the direct absorption of drugs and nutrients. However, determining the in vitro dissolution (i.e. how much drug dissolves in it and how quickly) will help you understand the role of gastric fluid in the overall in vivo dissolution process for a given medicine before a meal is eaten.

Fasted stomach fluid is simulated by the biorelevant medium FaSSGF (Fasted State Simulated Gastric Fluid).

2.           Fasted small intestinal fluid

After taking a medicine with a glass of water, fasted small intestinal fluid is made up of the drug and fluid received from the fasted stomach (see above) mixed with fluids already present in the small intestine and also secreted from the gall bladder. In healthy humans, fasted small intestinal fluid has a high pH compared to fasted stomach fluid because it is almost neutralized by juices secreted from the gall bladder. The resultant fluid contains a moderate level of physiological surfactants (bile salts, fats) and salts. These physiological surfactants can play a very significant role in how a drug is absorbed in the fasted state because they are able to dissolve drugs not readily soluble in water.

Small intestinal fluid plays a crucial role in the absorption of nutrients and drugs. You should therefore carry out dissolution studies in fasted simulated small intestinal fluid to help you understand the in vivo dissolution process for a drug before a meal is eaten.

Fasted small intestinal fluid is simulated by the biorelevant medium FaSSIF (Fasted State Simulated Intestinal Fluid).

3.           Fed stomach fluid

After taking the dosage form with a meal, the first important contact fluid that a drug encounters is fed stomach fluid. This is composed of the food and liquid that has been swallowed with the drug and the acidic gastric fluid already present in the fasting stomach. In healthy humans, it has a comparatively high pH compared to fasted gastric fluid. Fed gastric fluid also contains low levels of physiological surfactants refluxed back into the stomach from the top section of the small intestine as the stomach pylorus (gate) opens.

Fed gastric fluid is much more complex than its fasted state equivalent as it contains the food and certain breakdown products of digestion. The pH starts at around 6 and falls as gastric fluid is secreted and the stomach empties its contents into the small intestine. Average pH immediately after a meal can vary depending upon meal contents and individuals but halfway through reaches about pH4.5 and towards the end of emptying is around pH3.

Fed stomach fluid is simulated by the biorelevant media FEDGAS (Fed State Gastric Fluid) which is available at 3 pH’s: 6, 4.5 and 3.

4.           Fed small intestinal fluid

Fed small intestinal fluid is made up of the medicine and fluid containing the meal that has been received from the fed stomach. This is also mixed with fluid already present in the small intestine and juices secreted from the gall bladder. In healthy humans, fed small intestinal fluid has a much higher level of physiological surfactants because of the greater volume of juices secreted from the gall bladder during a meal. The resultant fluid contains a high level of physiological surfactants (bile salts, fats) and salts which can play a very significant role in how a drug is absorbed. This is because they can dissolve drug not readily soluble in water or even in fasted small intestinal fluid. Fed small intestinal fluid plays a crucial role in the absorption of nutrients and drugs. Running dissolution studies in it will help you understand the in vivo dissolution process for a given medicine with or after a meal.

Fed small intestinal fluid is simulated by the biorelevant medium FeSSIF (Fed State Simulated Intestinal Fluid).