Aqueous Solubility Assays
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Drug solubility measurement serves as a critical element in drug development and quality control because it affects absorption rates, bioavailability levels, therapeutic effectiveness and safety assessments. Low solubility drugs require larger doses or more frequent dosing to maintain therapeutic levels which increases the patient's medication load and elevates the chances of side effects. The development of low-solubility formulations demands the use of advanced techniques which results in additional technical complexity and higher development costs to solve solubility and stability issues.
Creative Bioarray provides clients with high-throughput solubility assessment services that include kinetic and thermodynamic solubility tests. The services facilitate researchers to identify and address solubility issues at early development stages which ensures maximum compound performance during key phases and accelerates the path to market entry.
Creative Bioarray's Aqueous Solubility Assays Service
Kinetic solubility assay
Fig. 1. Kinetic solubility assay (Kerns EH and Di L, 2005).
The Kinetic Solubility Assay is designed for early-stage drug discovery, providing rapid, high-throughput solubility evaluation. This method involves dissolving compounds in DMSO and diluting them into an aqueous buffer (pH=7.4), with turbidimetry (UV absorbance at 620 nm) used to detect precipitation. The assay requires only small sample amounts for effective early-stage screening of compound libraries to expedite potential drug candidate identification.
| Parameter | Conditions |
| Initial Concentration | 200 µM (standard) or adjustable per requirements |
| Aqueous Buffer | dH20 + 0.1-2% DMSO |
| Incubation Conditions | Room temperature or 37°C, up to 24 h |
| Sample Requirement | 10 mM DMSO stock solution |
| Analysis | HPLC-UV/LC-MS/MS |
Advantages:
- High Throughput: Automated workstation integration enables rapid analysis of hundreds of samples daily.
- Low Sample Consumption: Minimal compound requirement conserves R&D resources.
- Flexible Adaptation: Adjustable buffer pH and media to mimic diverse physiological environments.
Thermodynamic solubility assay
Fig. 2. Thermodynamic solubility assay (Kerns EH and Di L, 2005).
The Thermodynamic Solubility Assay establishes a substance's maximum solubility using saturated solution equilibrium and stands as the definitive benchmark for solubility measurement. Solid compounds undergo agitation with buffer for 24 hours to achieve equilibrium. After filtration the dissolved concentrations are measured by HPLC-UV or LC-MS/MS. This method is an essential tool in late-stage lead optimization and formulation development because it produces precise and dependable data.
| Parameter | Conditions |
| Initial Concentration | 4 mg/mL (standard) |
| Aqueous Buffer | dH20 or buffered solution |
| Incubation Conditions | Room temperature or 37°C, 24 h |
| Sample Requirement | 2 mg solid (testing) + 1 mg (standard curve preparation) |
| Analysis | HPLC-UV/LC-MS/MS |
Advantages:
- High Accuracy: Simulates equilibrium conditions to reflect solubility in real physiological environments.
- Broad Applicability: Supports testing of crystalline, amorphous, and liquid compounds for diverse R&D needs.
- Formulation Support: Provides solubilization strategies for low-solubility compounds.
Features
Advanced Detection Equipment
Equipped with high-precision instruments such as PLC (High-Performance Liquid Chromatography), and dissolution testers, we ensure the accuracy of test results.
Expert Technical Team
Our team of experts, with extensive experience in pharmaceutical analysis, offers end-to-end services ranging from method development to data interpretation.
Flexible Service Models
Testing conditions are tailored based on compound properties (e.g., pKa, lipophilicity) to optimize data relevance.
FAQ
1. What is the difference between kinetic and thermodynamic solubility assays?
During early discovery scientists use kinetic solubility assays to assess how compounds dissolve when they transition from organic solvents like DMSO to aqueous solutions. Thermodynamic solubility assays applied during late-stage development evaluate a compound's maximum solubility under equilibrium conditions. We recommend using kinetic testing to narrow down candidates first, followed by thermodynamic validation for prioritized compounds.
2. What key factors should be considered when measuring solubility?
Solubility determination is influenced by multiple factors, including:
- pH value: Solubility of ionizable compounds is highly pH-dependent (e.g., weak acids dissolve better in alkaline media).
- Temperature: Thermodynamic solubility requires equilibration at controlled temperatures (e.g., 25°C or 37°C).
- Compound form: Crystalline, amorphous, or salt forms may significantly impact solubility.
- Solvent selection: DMSO residues may interfere with kinetic assay results.
- Ionic strength and buffer composition: Bio-relevant buffers (e.g., simulated intestinal fluid) must align with real-world applications.
3. How can low-solubility compounds be optimized for testing?
- Solubilization strategies: Add surfactants (e.g., Tween 80), cyclodextrin complexation, or nanoparticle formulation technologies.
- Media adjustment: Select bio-relevant media (e.g., FaSSIF/FeSSIF) based on the target administration route (oral, injectable, etc.).
- Data interpretation: Evaluate structural modifications using physicochemical parameters (e.g., LogP, pKa) to enhance solubility.
4. Does low sample purity affect test results?
Yes. Impurities may interfere with detection (e.g., overlapping UV absorption peaks) or compete with the main component for dissolution. We recommend providing samples with ≥95% purity (HPLC-verified). If impurities are present, their potential impact should be noted in the report.
Reference
- Kerns EH., and Li D. Automation in pharmaceutical profiling. JALA: Journal of the Association for Laboratory Automation 10.2 (2005): 114-123.
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