Aqueous Solubility Assays

Aqueous solubility is one of the most critical properties of therapeutic compounds. The solubility of compounds will directly affect the ADME and pharmacokinetic (PK) properties of drugs. Insoluble or poorly soluble compounds generally have low bioavailability, high plasma protein binding, and tend to precipitate from the solution when measured in vitro. BOC Sciences offers comprehensive in vitro ADME and PK services, including compound water solubility testing, designed to help clients identify compounds with limited solubility. We are also working on strategies to address multiple solubility limitations.

Fig. 1 Applications of solubility data

The morphology of drugs is also an important issue to be considered in the formulation development stage, and the solubility of drugs is the basic considerations for the design of pharmaceutical preparations. For example, solid formulations are generally preferred over liquid formulations because they are more chemically stable, easier to process, and easier to deliver. However, solid drugs must be dissolved before they have therapeutic activity after entering the body. In addition, the stability and solubility of the drug also have a significant impact on the drug delivery process. Unknown solubility may cause problems with drug absorption following oral administration. Therefore, the solubility properties of compounds have a crucial impact on drug formulation development, drug delivery, and drug modes of action.

Solubility is not only the limiting factor for the freely interacting fraction of compounds in gastrointestinal fluids, plasma, and other matrices in vivo, but is also used to plan reliable test conditions for other in vitro assays. With state-of-the-art equipment and scientific expertise in ADME, BOC Sciences focuses on providing a full suite of compound solubility services, including water solubility testing in various simulated fluids using multiple techniques.

Kinetic Solubility Assays

Kinetic solubility assays simulated early in vitro screening conditions for compounds, namely dissolution in DMSO. Therefore, kinetic solubility assays are particularly useful in the early stages of drug discovery. In general, kinetic solubility assays has the characteristics of fast, low sample requirement and high cost performance. The test sample needs to first be dissolved in a DMSO stock solution and then added to a specific aqueous buffer. Solubility measurements were performed using LC-MS/MS or HPLC-UV after filtration after incubation at specific temperature and time conditions. Since most compounds contain ionizable groups, this assay can be used to determine the solubility of compounds in any matrix or pH.

Thermodynamic Solubility Assays

Typically, thermodynamic (or equilibrium) solubility primarily measures the solubility of solid compounds as equilibrium saturated solutions in aqueous solvents. Since solid materials are not commonly used in early drug screening, thermodynamic solubility assessment is primarily used in late drug discovery/early development. For thermodynamic solubility testing, aqueous solvents are first added to excess of solid compounds. Then, long-term incubation are performed to ensure lysis equilibrium. DMSO stock solution are quantified using HPLC-UV or LC-MS/MS after filtration or centrifugation to remove insolubles.

In addition to conventional kinetic solubility assays and thermodynamic solubility assays, BOC Sciences is committed to developing new strategies to effectively increase solubility, including adding ionizable groups for structural modification, reducing lipophilicity (LogP), reducing molecular weight, introducing hydrogen bond donors and acceptors, designing prodrugs, and adding polar groups. In addition, we have the ability to improve the solubility of poorly soluble drugs through strategies such as particle size reduction, preparation of salt forms, and the use of surfactants. If you are interested in our aqueous solubility assay services, please contact us to learn more.