Kinetic & Thermodynamic Solubility Testing
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Solubility Studies for Your Drug Candidate
Solubility plays a critical role in guiding compound selection and optimization during drug discovery. Solubility influences various pharmacokinetic properties, including absorption, distribution, metabolism, and excretion, and ultimately impacts the overall efficacy of a drug compound. Performing solubility screens early on helps to quickly identify and remove compounds that may fail due to poor absorption or low bioavailability, saving the cost of more expensive screens later on.
Therefore, the determination of solubility values should be prioritized as early as possible during drug development to enable informed decision-making and improve the chances of identifying promising drug candidates. WuXi AppTec helps you build an in vitro ADME program that includes the correct solubility assays and provides the data you need for successful regulatory submission.
Expert Solubility Testing Partner
WuXi AppTec is an experienced preclinical testing partner, conducting more than 300,000 in vitro studies every year. We have extensive experience conducting kinetic and thermodynamic solubility studies and can help you develop an in vitro ADME program for your specific drug candidate.
Kinetic Solubility Testing
Kinetic solubility testing (Table 1) is used to evaluate the solubility of a compound that is already fully dissolved in an organic solvent, typically DMSO. A small percentage of this organic solvent is introduced into an aqueous solution, and the precipitation of the compound is measured across various concentrations. Kinetic solubility testing is usually conducted during the early stages of drug discovery, including lead identification and lead optimization, to guide the selection of promising drug candidates.
Table 1: Kinetic Solubility Method
| Theoretical Concentration | 200 µM |
|---|---|
| Theoretical Concentration | 200 µM |
| Media | Aqueous buffer system, such as 50 mM phosphate buffer solution, pH 7.4; bio-relevant media, such as simulated gastrointestinal fluid |
| Percentage of DMSO | 2% (routine), adjustable to 1% |
| Incubation Equilibration Time | 24h |
| Equilibration Temperature | Room temperature or 37°C |
| Compound Required | 100 µL of 10 mM DMSO stock solution |
| Analytical Method | HPLC-UV/LC/MS/MS |
| Turnaround Time | 5 working days |
Thermodynamic Solubility Testing
Thermodynamic solubility testing (Table 2) is used to measure the maximum concentration of a drug compound that can be dissolved in a solvent under equilibrium conditions. This study is typically conducted during the later stages of preclinical drug development, after promising compounds have been identified and optimized for activity and selectivity.
Table 2: Thermodynamic Solubility Test Method
| Theoretical Concentration | 200 µM |
|---|---|
| Sample Amount | 2 mg solid (for solubility experiments) and 1 mg solid (for linearity curves preparation) |
| Media | Aqueous buffer system, such as 50 mM phosphate buffer solution, pH 7.4; bio-relevant media, such as simulated gastrointestinal fluid |
| Incubation Equilibration Time | 24h |
| Equilibration Temperature | Room temperature or 37°C |
| Analytical Method | HPLC-UV/LC/MS/MS |
| Turnaround Time | 5 working days |
Other Solubility Studies
In addition to kinetic and thermodynamic solubility testing, other types of solubility testing that may be conducted during drug discovery include pH-dependent solubility testing, lipophilicity, solid-state characterization, etc.
Kinetic & Thermodynamic Solubility Testing FAQ
Why is drug solubility testing necessary?
Solubility plays a critical role in guiding compound selection and optimization during drug discovery. Solubility influences various pharmacokinetic properties, including absorption, distribution, metabolism, and excretion (ADME), and ultimately impacts the overall efficacy of a drug compound. Conducting a solubility screen at an early stage allows for the timely identification and elimination of compounds that are prone to failure due to inadequate absorption or low bioavailability. Therefore, the determination of solubility values should be prioritized as early as possible to enable informed decision-making and improve the chances of identifying promising drug candidates.
What is kinetic solubility testing?
Kinetic solubility testing is used to evaluate the solubility of a compound that is already fully dissolved in an organic solvent, typically DMSO. A small percentage of this organic solvent is introduced into an aqueous solution, and the precipitation of the compound is measured across various concentrations.
What is thermodynamic solubility testing?
Thermodynamic solubility testing is used to measure the maximum concentration of a drug compound that can be dissolved in an aqueous buffer system or bio-relevant medium under equilibrium conditions.
When should I start kinetic & thermodynamic solubility testing?
Conducting solubility screens at an early stage allows for the timely identification and elimination of compounds that are prone to failure due to inadequate absorption or low bioavailability. Kinetic solubility testing is typically conducted during the early stages of drug discovery, including lead identification and lead optimization, to guide the selection of promising drug candidates. Thermodynamic solubility testing is typically conducted during the later stages of drug development to optimize drug formulations and predict in vivo behavior.
What controls are used in kinetic and thermodynamic solubility assays?
Conducting solubility screens at an early stage allows for the timely identification and elimination of compounds that are prone to failure due to inadequate absorption or low bioavailability. Kinetic solubility testing is typically conducted during the early stages of drug discovery, including lead identification and lead optimization, to guide the selection of promising drug candidates. Thermodynamic solubility testing is typically conducted during the later stages of drug development to optimize drug formulations and predict in vivo behavior.
What is the turnaround time for solubility testing?
Solubility studies are generally considered standard and straightforward experiments. The turnaround time can range from one to a few days, depending on the study’s specific requirements.