Filtering out inefficiencies in dissolution testing
In the grand scheme of dissolution testing, filtration may seem a small step along the way, but this perception could not be further from the truth. The right choice of membrane filters can drive efficiencies right along the process, from extending high performance liquid chromatography (HPLC) column life and cutting instrument maintenance costs to reducing time-consuming retests, all while giving laboratories confidence in the quality of their results.
This resource explores:
- The benefits of choosing the right filter (including reduced instrument maintenance costs, fewer time-consuming retests, and more)
- How the right filter can ensure good sample preparation and sample integrity
- How to choose the right filter or membrane media for your workflow
In today’s increasingly expanding pharmaceutical environment, can your organization really afford not to take a closer look at filtration?
Download the free resource now to learn more about how to choose the right filter, courtesy of Cytiva.
Filtering out inefficiencies in dissolution testing:
How the right filter can save pharma laboratories time and money
In the grand scheme of dissolution testing, filtration may seem a small step along the way, but this perception could not be further from the truth.
The right choice of membrane filters can drive efficiencies right along the process, from extending High Performance Liquid Chromatography (HPLC) column life and cutting instrument maintenance costs to reducing time-consuming retests – all while giving laboratories confidence in the quality of their results.
In today’s increasingly expanding pharmaceutical environment, then, can your organization really afford not to take a closer look at filtration?
A small but far from insignificant consideration
Dissolution testing, which measures the rate at which an active pharmaceutical ingredient (API) is released from a solid dosage form as it dissolves, is an integral part of a dissolution laboratory’s daily work. Filtration removes undissolved API from the sample, so it doesn’t erroneously contribute to the calculation of the API release rate. Whether testing is conducted as part of the drug development process or before drug market release, the information gleaned from this procedure is essential for quality control (QC) and to ensure regulatory compliance.
The pharmaceutical sector has seen costs increase in recent years, meaning teams are always looking for ways to drive efficiencies. A key step early in the dissolution process, is the selection of the appropriate membrane or filter media, which has a high impact on the accuracy of the final analysis. Proper filtration will protect HPLC instruments against particulate contamination, avoiding downtime, extending equipment life, and lowering overall costs.
Another consideration to improve efficiency is the level of automation that may be used to accelerate throughput or increase accuracy of results.
At Cytiva, we believe getting the basics right makes a difference. Something as comparatively simple as choosing the right membrane filter during dissolution testing can provide reliability of test results, whether the workflow is manual, semi, or fully automated.
Good sample preparation
Drug dissolution testing is a routine QC test that assesses the batch-to-batch consistency of tablets, pills, and capsules before market release. Scientists also use it in drug development to predict in vivo behaviour and develop release profiles of different formulations.
Scientists determine the amount of API dissolved at different times by withdrawing samples from the dissolution vessel at pre-defined time stamps. Filtration stops the dissolution process by screening out the undissolved drug particles and any excipients, ensuring
an accurate representation of that single and specific time point during dissolution. This enables sample analysis to occur to determine the amount of drug dissolved.
Filtration, either through cannula filters at the tip of sample probes, glass filter circles, or via in-line syringe-type membranes, is key in sample preparation.
The process, which is detailed in regional pharmacopeia’s and is required by regulators, has four key steps: dissolution, sample collection, sample preparation, which includes filtration, and analysis.
Particulate contamination and sample integrity
If impurities are not effectively removed from the sample during preparation, they may clog the column and damage instrumentation, as well as lead to ambiguity in results and avoidable retesting.
During drug development, lack of sample integrity can affect data reliability. This can elongate already lengthy clinical research timelines, delay time to approval, and drive-up costs. In some cases, it may even contribute to study failure.
Low sample integrity, and the subsequent need for re-tests delays batch release, making hold ups expensive. More importantly, though, they restrict access to the medications people depend upon.
Fortunately, correct membrane selection enhances preparation processes, avoiding particulate contamination and protecting sample integrity and instrumentation, while heightening QC compliance.
Selecting the right filter membrane or media
What are the main considerations when matching the right membrane or media to the sample preparation workflow in hand?
Choose a depth filter containing only glass fibre when the dissolution media contains a large amount of coarse particulates.
Choose a membrane filter when the number of coarse particulates in the dissolution media is low.
Choose a combined depth and membrane filter when a standard depth filter does not provide a clear filtrate and/or a membrane filter gets clogged.
Chemical compatibility
Teams should validate their filter media to the pH, ionic strength, and surfactant of their sample. Membranes with broad chemical compatibility, such as regenerated
cellulose, Hydrophilic PTFE and PVDF, can help reduce the workload of this step.
Adsorption
Dissolved API material should not be adsorbed into the filter when clarifying, as it leads to errors in quantitation. It’s worth noting that regenerated cellulose and glass fibre membranes provide lower adsorption properties.
Detection of analytes
This can become an issue if analytes are detected at the same wavelength as the API or any extractables in the sample. Sampling and testing multiple membrane types is best to determine the optimal detection performance. Using filter materials with low levels of extractables, such as regenerated cellulose Or Hydrophilic PTFE can avoid this kind of interference.
Interference
Excipient load or the volume of non-API particulates remaining in the formulation after dissolution. To avoid extraneous particles and maintain filtration efficiency, Scientists should select a filter with capacity to handle a high excipient load, such as Whatman GD/X™ or, in the case of automated dissolution systems, Whatman™ Roby syringe filters with glass fibre prefilter.
Below are other attributes that should be investigated when selecting the optimal membrane and media for your filtration.
Filtration and 21st century science
The multiple sampling and sample preparation steps make dissolution testing ideal for automation.
Many pharma laboratories have embraced automation for some or all of the workflow, from the preparation and dispensing of dissolution media and the introduction of the dosage form, to sampling, sample preparation, and data collection and analysis.
In short, automation, whether that be semi- or full automation, is a fast-growing trend in a sector constantly on the lookout for new ways to drive productivity. Removing the need for scientists to continuously perform manual tasks, such as withdrawing samples at pre-defined time points, frees them up to concentrate on other tasks and reduces human error, improving throughput.
It’s a move that brings new considerations to the fore. Syringe filters’ polypropylene housing must be dimensionally compatible with the automated dissolution systems to ensure smooth transportation from the storage turntable to the filtration site. The ease and frequency of filter replacements between timepoints are another important factor.
Filter out inefficiencies
As a high-tech, high-cost sector, the pharmaceutical industry is constantly looking for innovation. Yet it’s important to remember that innovation is not always about the big- ticket items, such as expensive, advanced equipment and automated systems. Rather, it starts with the basics.
Correct membrane and media selection is a crucial step in the dissolution testing workflow. Get the basics right and everything will follow – because sometimes the simplest solutions can have the biggest impact.
With the Whatman™ range, Cytiva combines the widest portfolio of filtration products available on the market with extensive, in-depth knowledge of the dissolution and filtration processes. Speak to us to discover which membrane is right for you and start reaping the benefits of increased productivity today.
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