Solubility measurements can be performed by three methods: µDISS Profiler™ and Modified Shake Flask and Potentiometric Titration.
| Which Method is Best? |
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When solubility methods are considered, the final selection depends on the budget, sample availability and the data desired. As expected, each method offers different advantages. In general, the Modified Shake Flask is the most cost-effective way to determine the solubility of many samples at different pHs after overnight equilibration at room temperature, although the upper limit depends on the starting concentration of the API stock solution. The µDISS Profiler™ is best suited for determining the concentration during equilibration, thus providing very detailed dynamic information. And with more flexibility in using buffers and sample size, the upper limit is higher than with the Modified Shake Flask. Using potentiometry, the Gemini Profiler™ determines the solubility of the uncharged, neutral species and calculates the pH-solubility curve based on the Henderson-Hasselbalch equation. The solubility of the salt species cannot be extrapolated.
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Method Properties
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µSOL Modified Shake Flask
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µDISS Profiler
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Potentiometric Gemini Profiler
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Quantitation
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direct UV
230-500 nm
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direct UV
215-450 nm
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potentiometric
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Filtration of excess solids required?
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Yes
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Spectral correction
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No
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Concentration vs Time Curves?
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single point only
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Yes
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No
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Typical Replicates per run
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3
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2
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3
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Samples and/or pH values per run
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< 28
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3
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NA
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Temperature
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ambient only
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10-40°C
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23-40°C
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Buffer types
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Prisma HTTM
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PrismaTM, USP, FaSSIF, FeSSIF, others
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Titration in
0.15 N KCl
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Upper Solubility Limit, approx.
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0.1-0.2 mg/mL
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10 mg/mL
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50 mg/mL
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Detection Limit
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0.1 µg/mL
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0.02 µg/mL
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0.005 µg/mL
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| µSOL Modified Shake Flask |
Solubility measurements are performed at specific pH values using a modified shake flask method. Stock solutions of the drug in DMSO are diluted with aqueous, non-phosphate buffer solutions to contain <1% DMSO. For equilibrium solubility, the solutions are allowed to incubate at least 15 hours; kinetic measurements available upon request. The solutions are then filtered and quantified with UV spectrophotometry incorporating pION peak shape analysis, which indicates impurities or decomposition problems. This technique has a lower limit of solubility at 0.1 µg/mL and an upper limit of solubility, usually between 100-200 µg/mL. The method is suitable for any compound with a UV chromophore.
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To submit your compounds for analysis:
- Complete a Sample Submittal Form and Sample Input Template for each compound.
- Include the forms in the sample shipment.
- Submit either a 100 µL of a 10-100 mM solution in DMSO, or 5-7 mg solid
- Incomplete forms will delay sample turnaround.
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| µDISS Profiler™ |
| This method monitors the real time concentration of drugs using fiber optic probes with UV photodiode arrays. Spectral fingerprints from 200-450 nm are aquired as rapidly as every 5 seconds, allowing observation of dynamic solution equilibria brought about by formation of metastable species. Both dissolution and solubility can be determined in one run. |
- To discuss your needs and requirements, contact pION.
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| Gemini Profiler™ Potentiometric Titration |
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This measurement of solubility is comparable to the "shake-flask" technique as determined by the FDA. The potentiometric method requires an accurately measured pKa. Titrations are performed using dilute acid or base titrants in 0.15 M KCl ionic strength buffered solutions.
Although solubility of the salt is not determined with this technique, we provide the solubility-pH profile over the entire pH range excluding the onset of salt precipitate.
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| To submit your compounds for analysis: |
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