The Importance Of Fasted + Fed States
Explaining the difference between ‘fasted’ (without food) and ‘fed’ (with food) states and how they impact on the solubility and dissolution of a drug.
What are the ‘fasted’ and ‘fed’ states?
The fasted state refers to the conditions of the gut fluids before a meal whilst the fed state refers to the conditions of the gut fluids after a meal. In humans the concentration of natural surfactants (such as bile salts and phospholipids) that can improve drug performance are typically much higher in the fed state than the fasted one.
What is the impact of fasted and fed states on oral drug development?
The difference in concentration of natural surfactants, bile salts, phospholipids and enzymes can have a big impact on a compound’s dissolution profile (how quickly it dissolves) and its apparent solubility (the maximum dissolved concentration in the gut fluid). For poorly water soluble compounds, performance can be improved in the fed state. So it’s important to test in both fed and fasted Biorelevant Media and choose the right formulation development path to obtain a final drug product that performs well.
Selecting fed and fasted Biorelevant Media for poorly soluble compounds
Poorly water soluble drugs, with a higher affinity for fatty molecules than water (lipophilic compounds), can display improved performance (higher dissolution rates and greater solubility) in the fed vs. the fasted state. Typically fasted and fed state intestinal Biorelevant Media (FaSSIF and FeSSIF) are used for immediate release neutral and acidic compounds. For bases, gastric media (FaSSGF and FeSSGF) is also necessary as they could precipitate when moving from the low pH of the stomach to the higher pH of the intestine.
Fasted Biorelevant Media selection for highly soluble compounds
Highly water soluble drugs are more straightforward. For immediate release neutral and acidic compounds, testing solubility and dissolution in fasted state intestinal Biorelevant Media (FaSSIF) is recommended. For bases, additional testing in fasted state simulated gastric media (FaSSGF) is required to identify precipitation issues.
The take-home message
Fed and fasted states can have a huge influence on oral drug delivery, with the fed state potentially improving the performance of poorly soluble drugs. Knowing your oral drug’s chemistry is crucial to understanding whether fed and fasted states can affect its performance. Our easy to use Biorelevant Media could greatly assist you during the various stages of drug development.