Why is biorelevant solubility so important?
Biorelevant solubility is one of the most important physiochemical properties to know when developing an orally administered drug molecule. It reveals how much drug is likely to dissolve within the intestinal fluids or, in other words, the concentration of soluble drug that is in the intestinal fluids. As explained in the Biopharmaceutical Classification System, solubility in combination with permeability influences the amount of drug that can be absorbed. This fundamental in vitro information can then be used to calculate an estimate of how much of an expected dose will dissolve in vivo.
Understanding the biorelevant solubility of a new drug can help compound selection, selection of the physical form (salt or polymorph) and pre-clinical formulation development. It can indicate if a formulation to increase drug solubility may be needed. If the drug has low solubility in Biorelevant Media, it can also predict how risky the development challenge would be if the drug were selected as a clinical development candidate. New drugs that are difficult to formulate take considerably longer and have much higher development costs.
For generic drugs, biorelevant solubility tests are generally much less important because the drug has already been commercialised. It is therefore known that the solubility of the drug product is sufficient to make the drug absorbable. In these cases, it is more typical to start with biorelevant dissolution tests.
When should biorelevant solubility tests be performed?
It is most beneficial to carry out these simple tests on an unformulated NCE drug substance before starting formulation development. Profiling your NCE’s biorelevant equilibrium solubility during preformulation studies can provide the necessary information to help guide the compound’s development.
Which Biorelevant Media should I test in?
Media selection depends upon the aim of your test. First of all, decide if you want to study the solubility of the drug in fasted (without food) state, fed state (with food) or both conditions. Fasted state media (e.g. FaSSIF) are usually measured because the fasted state is the benchmark condition for most drug dosing studies. This is because it is more convenient to administer a dosage form after drinking a glass of water and without eating food.
However, if you also want to establish drug solubility in the presence of food, then testing in media that simulate fed state fluids is also important. For drugs with low water solubility, to support labelling claims it is mandatory that clinical studies exploring the effect of food on drug exposure is carried out. Preliminary fed state solubility results can provide an early indication if your drug could be affected by the intake of food before you carry out the first fed state clinical trials.
Why is the location of the gastrointestinal fluids important?
You can also decide which Biorelevant Media to use based on the gastrointestinal fluid location you want to study. Although drug absorption can occur throughout the gastrointestinal tract, most of the dose of an immediate release drug is usually absorbed in upper small intestinal fluid because of the larger surface area available for absorption. Therefore, knowing the drug solubility in media that simulate small intestinal fluid (FaSSIF) is typically most important for any drug intended for immediate release.
How do I conduct a biorelevant solubility test?
A biorelevant solubility test is very easy to do. It’s similar to a study that you would carry out for measuring drug solubility in water. You simply use the Biorelevant Media of your choice instead of water. If you would like to find out more about these tests please contact us.