Biorelevant Filters (GMF13), 0.45 µm pore size, 13 mm diameter are recommended for separating undissolved drug from biorelevant dissolution samples.

These filters are designed to minimise drug adsorption while maintaining high separation efficiency from biorelevant samples through a specially designed built-in prefilter. This filter typically shows a significantly lower level (approximately 3 to 4-fold lower) of drug adsorption than an equivalent 25mm filter.

These unique filters provide the following technical benefits:

•         a low sample volume is typically required to saturate the filter

•         built-in prefilter enables efficient filtration with minimal risk of clogging

•         low drug adsorption and negligible extractables

•         quick and easy filtration

•         25 mm casing enables ease of handling

•         Every batch comes with a Certificate of Conformity.

These benefits enable sample volumes of 5 mL or less to be rapidly filtered. The typical recommended volume for each sampling time point is approximately 5 mL.

If you wish to carry out filter adsorption for a specific drug or formulation, a filter adsorption study can be performed as described in the next post.

Filter adsorption studies are determined whether the drug is adsorbed onto a filter during dissolution sample filtration. Filter adsorption can lead to underestimation of dissolution results.

If filter adsorption occurs, you need to saturate the filter with sufficient sample so that further sample filtrate is no longer significantly affected by drug adsorption.

As with any dissolution medium, the filter adsorption sample should be prepared at a concentration representative of the expected drug concentration at the first nominal dissolution sampling time point. For example, this may correspond to approximately 10% or 20% drug release, depending on the expected early dissolution profile.

The filter adsorption study may then be typically performed using the recommended procedure shown below with at least 3 filters.

Dilute the unfiltered and filtrate samples and analyse by HPLC. 

Determine the percentage of drug adsorbed onto the filters for EACH medium used and establish the total dissolution sampling volume required at each time point. The total sampling volume should include both the filter saturation/discard volume and the sample filtrate volume required for analysis.

The percentage of drug adsorbed may be calculated using:

% Adsorbed = [(Average AUC of unfiltered sample − Average AUC of filtered sample) / Average AUC of unfiltered sample] × 100

The filtration fraction that shows acceptable filter saturation/recovery, low % adsorbed, and acceptable %RSD can be used to define the minimum discard volume required to saturate the filter before collecting the dissolution sample for analysis.

For example, if acceptable saturation is achieved after filtering and discarding 4 mL, then the total dissolution sampling volume should include:

4 mL discard volume + 1 mL required analytical sample volume = 5 mL total sampling volume

If acceptable filter saturation/recovery is not achieved, a larger discard volume may be required before collecting the sample for HPLC analysis.

A single stage biorelevant dissolution setup is similar to using a typical dissolution setup using QC medium.

The parameters typically used are described below.

However, media, sampling intervals/timepoints and the criticality of analysing diluted dissolution samples differ. These aspects are descibed in the following posts.

Filter

A significant benefit of using Biorelevant GMF13 filters is that drug adsorption is minimal and therefore filter saturation can be built into the sampling regimen making the whole dissolution experiment and filtration easy. Lower sample volumes (than the recommended 5mL, see below) may also be used if supported by a filter adsorption study.

Fresh filter

For accurate and precise dissolution results, it is highly recommended to use a fresh new filter at each sampling time point. This not only helps prevent clogging but minimises the risk of retained undissolved drug particles dissolving within the filter between sampling points. Using a fresh filter at each time point helps reduce variability in dissolution results.

Sampling volume

Typically, a 5 mL sample volume is recommended at each dissolution sampling time point. The sample at each time point is withdrawn from a dissolution vessel via cannula with a syringe attached.

The withdrawn sample in the syringe is immediately filtered through a Biorelevant GMF13 filter. During filtration, the first 4 mL of filtrate is used as the filter saturation/discard volume, and the final 1 mL of filtrate is collected for analysis.

Dilute

Each Dissolution sample should be immediately diluted before HPLC injection where required. The reason for sample dilution is explained here.

Discard

It is typically recommended to discard the 4 mL filtrate used for filter saturation without medium replacement. This keeps the total drug-to-medium ratio during biorelevant dissolution constant during the study.

Recommended sampling time points for a formulation that has not previously been explored in the fasted state biorelevant medium are:

For FaSSGF: 5, 10, 20, 30, 45, 60, 90 minutes

For FaSSIF: 5, 10, 20, 30, 45, 60, 90, 120, and 180 minutes

These time points help evaluate how the drug product behaves (dissolution and stability) in the biorelevant medium over physiologically relevant time frames. For immediate-release dosage forms, carefully observe and record the disintegration behaviour during the first 2 to 3 minutes.