The filter is a critical element in dissolution testing. Read on to see why and how filter choice can affect dissolution test accuracy, and TIPs for achieving accurate results.
Dissolution testing for drug release measures the rate at which the active pharmaceutical ingredient (API) is released from the solid dosage form as the tablet, pill or capsule dissolves. This drug release information is essential for pharma quality control (QC) and drug development.
The role of filtration in dissolution testing is to remove undissolved API from the sample, which stops the dissolution process, stabilizing the sample state and making sure it accurately represents a single and specific time point during dissolution. The dissolution sample is tested sequentially at specified times during the dissolution process. By analyzing the sequential samples, you can determine the rate of dissolution (release rate of the API). The test method, referenced in the US Pharmacopeia (USP) General Chapter 11 (2020), specifies that sampling and filtration must occur within ± 2% of each stated time point. Filtration is central to the test method.
Timing intervals: For accurate results, as well as regulatory compliance, sample must be withdrawn from the dissolution vessel at the specified intervals.
Regardless of whether testing is done for QC or during drug development, filtration needs are the same. The properties of your filter and how it interacts with your sample can affect the accuracy of your results in several ways.
Filter type: Throughput delays can affect accuracy by allowing more time for the API to dissolve in the sample. The wrong choice of filter media and pore size can lead to premature blockage of the filter device, which in turn causes throughput delays. This is more likely to occur with high particulate samples or samples with high excipient loads.
Filter type plays a key role in avoiding throughput delays. Three types of filter are available for dissolution testing:
- Use a glass fiber filter (depth filter) when the dissolution media contains a large amount of coarse particles.
- Use a membrane filter (surface filter) when the amount of course particulates is low.
- A stacked, or combination, filter combines a depth filter with a surface filter in one device. Try a stacked filter to get the combined functionality of both filter media.
Extractables: The presence of extractables in your sample can affect test results if they absorb light at the same wavelength as the API. To ensure test accuracy, use materials which have very low level of extractables such as Regenerated Cellulose or Hydrophilic PTFE.
Adsorption is the process in which the analyte adheres to the surface of the filter, rather than passing through. By validating your filter with the adsorption challenge, you can determine how much analyte is adsorbed onto the filter surface before the dissolution media flows freely through the filter. You then discard the initial amount of filtered dissolution media during testing to get an accurate measure of the dissolved analyte in the sample.
Filter efficiency for dissolution testing is the ability to remove undissolved API from a sample solution, while allowing dissolved API to pass through. Undissolved API in the sample may continue to dissolve, leading to innacurate results. If you are using HPLC for analysis, any undissolved particles can also cause damage to the column and shorten equipment life. Pore size is a key factor in filter efficiency.
Using the right filter for your method and analyte is key to accuracy in dissolution testing. Proper validation will not only help you select the most appropriate filter, but also help you fine tune your method. If you are working in a regulated environment – or developing a product that will be regulated – filter validation is required for compliance. The three challenges used to validate filters for dissolution testing are the efficiency challenge, the leachability challenge, and the adsorption challenge.