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US 2004/0168529 A1Published application
Methods and systems for dissolution testing
AssigneeSymyx Technologies, Inc.
InventorsEric D. Carlson, Miroslav Petro, Son Hoai Nguyen
Life of this patent
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Abstract
Methods and systems for determining a dissolution profile of a sample material, and for solubilization screening of a library defined by an array comprising multiple sample materials are disclosed. The methods and systems are particularly advantageous for sampling and evaluation of very small samples, and can be advantageously applied in connection with evaluation of drug candidates.
Claims85
A method for determining a dissolution profile for a sample material, the method comprising
- dissolving at least a portion of the sample material in a solvent over a period of time to form a solution, the period of time defining a dissolution period, the solution having a concentration of the sample material that varies during the dissolution period,
- sampling a portion of the solution at least twice during the dissolution period, the solution being sampled at a first time within the dissolution period to obtain a first aliquot of the solution, and at a later second time within the dissolution period to obtain a second aliquot of the solution,
- subsampling a portion of the first aliqout of the solution to obtain a first sub-aliquot of the solution,
- determining the concentration of the sample material in the first sub-aliquot of the solution,
- subsampling a portion of the second aliqout of the solution to obtain a second sub-aliquot of the solution, and
- determining the concentration of the sample material in the second sub-aliquot of the solution.
3 more elements
A method for generating data defining a dissolution profile for a sample material, the method comprising
- dissolving at least a portion of the sample material in a solvent over a period of time to form a solution, the period of time defining a dissolution period, the solution having a concentration of the sample material that varies during the dissolution period,
- sampling a portion of the solution at a first time within the dissolution period to obtain a first aliquot of the solution,
- subsampling a portion of the first aliqout of the solution to obtain a first sub-aliquot of the solution, such subsampling thereby also resulting in a remainder portion of the first aliquot,
- returning the remainder portion of the first aliquot to the solution,
- sampling a portion of the solution at a later second time within the dissolution period after the remainder portion of the first aliquot is returned to the solution, to obtain a second aliquot of the solution,
- subsampling a portion of the second aliqout of the solution to obtain a second sub-aliquot of the solution, such subsampling thereby also resulting in a remainder portion of the second aliquot,
- returning the remainder portion of the second aliquot to the solution,
- determining the concentration of the sample material in the first sub-aliquot of the solution, whereby a first data point of the dissolution profile is defined by association of the concentration determined in the first sub-aliquot with the first time, and
- determining the concentration of the sample material in the second sub-aliquot of the solution, whereby a second data point of the dissolution profile is defined by association of the concentration determined in the second sub-aliquot with the second time.
6 more elements
A method for determining a dissolution profile for a sample material, the method comprising
- combining not more than about 50 mg of a sample material with a solvent,
- dissolving at least a portion of the sample material in the solvent over a period of time to form a solution, the period of time defining a dissolution period, the solution having a concentration of the sample material that varies during the dissolution period,
- sampling a portion of the solution at least twice during the dissolution period, the solution being sampled at a first time within the dissolution period to obtain a first aliquot of the solution, and at a later second time within the dissolution period to obtain a second aliquot of the solution,
- determining the concentration of the sample material in the first aliquot of the solution, and
- determining the concentration of the sample material in the second aliquot of the solution.
2 more elements
A method for determining a dissolution profile for a sample material, the method comprising
- dissolving at least a portion of the sample material in the solvent over a period of time to form a solution, the period of time defining a dissolution period, the solution having a concentration of the sample material that varies during the dissolution period,
- sampling a portion of the solution at least twice during the dissolution period, the solution being sampled at a first time within the dissolution period to obtain a first aliquot of the solution, and at a later second time within the dissolution period to obtain a second aliquot of the solution, the difference between the first time and the second time being not more than about 2 minutes,
- determining the concentration of the sample material in the first aliquot of the solution, and
- determining the concentration of the sample material in the second aliquot of the solution.
1 more element
A system for determining a dissolution profile for a sample material, the system comprising
- a sample container for dissolving at least a portion of the sample material in a solvent over a dissolution period of time to form a solution that has a concentration of the sample material that varies during the dissolution period,
- an automated sampling probe for sampling a portion of the solution at least twice during the dissolution period, the solution being sampled at first and second times within the dissolution period to obtain first and second aliquots of the solution, respectively, the sampling probe having a distal end positionable in fluid communication with the solution in the sample container, and having a proximate end,
- a sub-sampling device in fluid communication with the proximate end of the sampling probe, the sub-sampling device being configured for subsampling a portion of each of the first and second aliquots of the solution to obtain first and second sub-aliquots of the solution, and
- an analytical unit for determining the concentration of the sample material in the first and second sub-aliquots of the solution.
1 more element
A system for automated sampling of small volume liquid samples, the system comprising
- a sample container for containing a liquid sample,
- an automated liquid handing system comprising a sampling probe, a robotic arm for translating the sampling probe, and a pump in continuous or selectable fluid communication with the sampling probe for providing a motive force at least for withdrawing a portion of the liquid sample into the probe to effect sampling, the sampling probe having a distal end and a proximate end, the distal end of the sample probe being positionable in fluid communication with the liquid sample in the sample container for sampling a portion of the liquid sample to obtain an sampled aliquot, and
- a sampling valve providing fluid communication between the proximate end of the sampling probe and the pump, the sampling valve being a multi-port sampling valve comprising a sample loop, the sampling valve being configured in a first selectable position for loading at least part of the sampled aliquot into the sample loop through a sampling flow path from the proximate end of sampling probe to the first pump, the sampling valve being further configured for discharging the contents the sample loop from the sampling valve as a sub-aliquot of the sampled aliquot.
Dependencies are inferred from the claim text.