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It has been demonstrated that replication of the composition of the gastrointestinal media improves the ability to predict in vivo performance of drug products. Therefore, much effort has been made to replicate in vivo gastrointestinal media to provide simulated fluids for solubility assessment. Four levels of simulation of luminal composition have been proposed ranging from simple to more complex [6]; these are outlined in Table 4.2.

During the drug development process, the level of complexity will increase to ensure that the measurements are appropriate to the risk assessment of the product. Often biorelevant media are first used just before the human clinical phase of development.

As well as the levels of media it is important to note that there are significant compositional changes from the stomach to small intestine to large intestine that also need to be addressed. Furthermore, the impact of food cannot be ignored thus several variations of simulated fluids are reported in the literature. Most data has come from matching composition to intestinal fluids taken from healthy adult volunteers. However, there is also a need to account for populations that may differ including those with diseases or at the extremes of age (see Chapter 13).

There are several papers that describe the characterisation of human intestinal fluids and translate these findings into simulated fluids for the fasted state [7–11] and for the fed state [10, 11].

The composition of commonly used media is presented in Table 4.3.

Table 4.2 An overview of the four levels of biorelevant media that can simulate the gastrointestinal luminal environment.

Level	Purpose
Level 0 media	Replicates pH using a simple buffer
Level 1 media	Replicates pH and buffer capacity
Level 2 media	Replicates pH, buffer capacity, osmolality and solubilisation capacity using bile salts, dietary lipids and digestion products
Level 3	Builds on level 2 by also incorporating proteins and enzymes In addition can be viscosity matched to in vivo fluid

Table 4.3 Composition of commonly used simulated intestinal media: fasted state simulated gastric fluid (FaSSGF); fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF).

	FaSSGF	FaSSIF	FeSSIF
pH	1.6	6.5	5.0
Bile salt (taurocholate) (mM)	0.08	3	15
Phospholipids (mM)	0.02	0.75	3.75
Sodium ions	34	148	319
Chloride ions	59	106	203
Phosphate ions		29
Acetic acid			144