Back to results
US 7,024,955 B2Granted
Methods and systems for dissolution testing
AssigneeSymyx Technologies, Inc.
InventorsEric D. Carlson, Miroslav Petro, Son Hoai Nguyen
Life of this patent
Estimating the term…
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.
Claims73
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 resulting in a remainder portion of the first aliquot,
- determining the concentration of the sample material in the first sub-aliquot of the solution,
- returning the remainder portion of the first aliquot to the solution,
- subsampling a portion of the second aliqout of the solution to obtain a second sub-aliquot of the solution resulting in a remainder portion of the second aliquot,
- determining the concentration of the sample material in the second sub-aliquot of the solution, and
- returning the remainder portion of the second aliquot to the solution.
5 more elements
The method of claim 22 wherein the sample material comprises a drug composition comprising one or more drug candidates and one or more excipients.
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, the dissolving including combining the sample material with the solvent in a container to initiate dissolution of the sample material in the solvent, at least one of the sample material or the solvent being provided to the container by an automated dispensing probe at an initiation time, to,
- using an automated sampling probe for sampling 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 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, including
- filtering the first aliquot of the solution during or after sampling to obtain a filtered first aliquot of the solution, and
- filtering the second aliquot of the solution during or after sampling to obtain a filtered second aliquot of the solution,
- subsampling a portion of the first aliquot 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 aliquot 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.
5 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 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, the dissolving including varying a property of the solvent over time 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 alipuot 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 aliquot 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 aliquot 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 aliquot 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 aliquot 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 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 fist 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 including a sampling valve 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
Dependencies are inferred from the claim text.