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Filter Equivalence Studies

Posted by Pam Bialiy on

The following article has been authored by John Heaney. 

Filtering is a required step in processing dissolution samples as it both stops the dissolution of larger particles by separating them from the sample and removes any material that may interfere with the analysis by UV/Vis spectroscopy, HPLC, or UPLC.  There are a plethora of materials, shapes, sizes, and porosities available to choose from to ensure that a filter is appropriate for a specific method.  In many cases it’s possible to find equivalent filters from other suppliers.  However, that equivalence needs to be proven, ideally during the development of the dissolution method.

There are several advantages to determining equivalent filters, especially during the method development phase.  The first is it helps ensure that a filter will always be available to the staff for performing the tests.  Without the right filters, a QC department may grind to halt, resulting in stopped shipments as the batch cannot be fully evaluated.  The second is that it can be a cost saving measure.  Finding a less expensive, but otherwise equivalent filter can add up to large savings over the course of a few years as each dissolution test will likely use 6 to 8 for each sample point.  In some cases where different brands of dissolution testers are present, it may be necessary to perform equivalence studies in order to ensure filters that fit one brand of dissolution tester/sampler are equivalent to a different style that is used on another brand of dissolution tester/sampler.

Simply picking another filter of the same style, porosity and material from a different manufacturer is not enough to justify equivalence.  There are other tests that must be done as filter manufacturing materials and processes may be different between manufacturers. 

Checking to make sure the filter is sufficient to the task of filtering the samples is probably the most important step.  A simplistic test for this is to filter samples with the filter, and measure them immediately after filtering, as well as a few hours later.  If the concentration has increased significantly, then the filter is not removing all the larger particles from the sample, and some dissolution is still continuing within the vial or test tube.  It would require choosing a new filter, possibly one with a smaller pore size.  In addition, you want to make sure your samples are clean enough for analysis.  A 10 µm is typically recommended for UV/Vis, though 0.45 µm is very common.  For HPLC, 0.45 µm is a requirement and for UPLC 0.2 µm is a requirement.  Failure to filter with a sufficient pore size can at best affect the results, or at worst cause clogs or damage to the equipment used for analysis.                                  

Any filter, whether the first to be used in a method or being added as an equivalent, should be tested to ensure that the filter is not absorbing the API.  If a filter is absorbing the API, then the actual concentration in the sample is not truly known.  A simplistic way to approach this is to develop a series of standards which bracket the range of concentrations expected for the dissolution test, and then measure the standards before and after filtering.  Ideally there should be no discernable change in the concentration.  This should of course be done with multiple filters of each type in the evaluation.

Another aspect is ensuring the filter is not releasing anything into the sample that will interfere with the analysis.  The easiest approach for this is to filter clean dissolution media, and perform measurements before and after filtering.  Ideally there would be no discernable differences between the media before and after filtering.  If there is a difference, an evaluation should be performed to ensure that peaks or absorbance readings will not overlap with the API and interfere with the analysis.

Filter equivalence studies do take some extra time to perform, but in the long run they can save a lab money.  This is through direct savings by sourcing less expensive filters, and indirect savings by acting as insurance against a supplier running out of filters.

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