HIF samples were collected from the duodenum (the first part of the small intestine) after volunteers consumed half of a standard FDA breakfast (toast, eggs, bacon, and milk). The collected HIF samples were analysed for their content of lipids, proteins, bile salts, and phospholipids; additionally, pH was measured.
Samples collected after a solid meal (half of the FDA breakfast) were compared with those collected after a liquid meal. The results showed that the composition of HIF depends on the type of food, with the greatest differences observed in the concentration of lipids, cholesterol, and proteins, as well as in the extent of lipid digestion. This suggests that both food type and pH can influence how well drugs dissolve and are absorbed in the body.
To study the indirect pH effect, the HIF samples were pooled based on the time after eating. The pH of each pool was adjusted to values between 4 and 7, covering the reported pH range in the small intestine. These samples were then used to assess the solubility of selected drugs across different pH levels.
Only poorly soluble, neutral drugs were tested as these are not directly affected by pH changes. Still, the results showed a strong pH effect on drug solubility, indicating that pH-induced changes in the colloidal structure of HIF can affect drug solubility even for neutral drugs. Interestingly, the pH at which drugs dissolved the most varied depending on whether samples were collected after a solid or a liquid meal.
Further analysis revealed that larger colloidal structures, which facilitate drug dissolution, formed at lower pH levels. These structures also differed between HIF samples collected after solid and liquid meals, indicating that the type of food can significantly influence drug solubility and the behaviour of intestinal fluids.
For comparison, similar tests were conducted using commercially available simulated intestinal fluids (SIF), commonly used in drug development. Adding sodium oleate, which mimics free fatty acids, to SIF showed a strong pH dependence: drug solubility increased by up to 100 times at acidic pH compared to SIF without oleate. This effect was more pronounced for the more hydrophobic drugs, likely because they dissolve better in the oily droplets that form at low pH.
However, the solubility patterns in real HIF remained quite different from those in SIF, even with modified SIF. This suggests that current laboratory models may not fully capture the complex behaviour of real intestinal fluids, particularly in terms of pH-related effects.
