Dissolution testing provides critical drug release information on solid dosage forms, essential for pharma QC and drug development Read about filtration’s key role in the process to improve throughput and reduce result variability.
What is dissolution testing?
Drug dissolution testing is a routine test used in the pharmaceutical industry to provide critical in vitro drug release profiles, evaluating the rate of release of an active pharmaceutical ingredient (API) from its dosage form.
This information is essential for pharmaceutical quality control (pharma QC) in assessing batch-to-batch consistency of solid dosage forms, such as tablets, pills and capsules. It is also useful in drug development for predicting in vivo behavior and release profiles of different formulations.
The test involves several key steps:
- Dissolution of a solid dosage form under controlled conditions in a dissolution vessel.
- Collection at specific time points.
- Sample preparation, including filtration.
- Analysis of each sample to determine the amount of drug dissolved at certain time points. Analysis tools include high-performance liquid chromatography (HPLC) and UV-vis spectrophotometry.
We talk about automated dissolution testing methods in a recent article from our knowledge center. In this blog, I’ll focus on the sample preparation stage and the importance of the filtration step for producing accurate and reproducible results.
Why is filtration important in dissolution testing?
The aim of any drug dissolution test is to determine the amount of API dissolved at chosen time points as samples are withdrawn from the dissolution vessel.
Filtration is key to this process as it stops the dissolution process, effectively freezing the sample state and making sure it accurately represents a single and specific time point during dissolution. Filtration separates the dissolved drug from the undissolved dosage components, enabling sample analysis that determines the amount of drug dissolved.
This downstream analysis is often carried out through HPLC or UV-vis spectrophotometry, so good sample preparation, including efficient filtration, is necessary for accurate results. Impurities can affect the analysis and might damage the HPLC column.
Despite the importance of the sample preparation stage, it’s often overlooked during method development and throughout dissolution testing. As a result, laboratories might not be using the most appropriate membrane filters for the job, and this could be influencing results.
What should I consider when choosing a filter for dissolution testing?
It’s often the case that the syringe filter you routinely use for dissolution testing is just the one that’s available in-house. But, evaluating potential filter membranes during method validation can help researchers optimize the technique before transferring the dissolution test process to the QC lab. This optimization can also help maximize result accuracy and reproducibility.
There are three key filter characteristics to consider when evaluating membranes:
- Does the membrane have a broad chemical compatibility, suitable for use with a variety of solvents and APIs?
- Is a good drug recovery possible because of low analyte/drug binding to the membrane?
- Does the membrane show a low level of extractables, to avoid introducing impurities into the sample?
For all HPLC analyses, chemical compatibility and low levels of extractables are important considerations for reducing the risk of new contaminants interfering with results, and determining that the membrane filter, the solvents and APIs being investigated are well-matched.
Hydrophilic PTFE membranes have broad chemical compatibility, and so are not likely to introduce extractable impurities into samples. They are also inert and have low levels of analyte binding, which helps maximize recovery from the membrane and avoid inaccuracies in API quantitation.
It’s also possible to use nylon membranes for dissolution testing, but they tend to have strong drug binding characteristics that might lead to inaccurate API quantitation. However, you can reduce the level of impurities and alleviate some of the drug binding by pre-rinsing the syringe filter. It’s possible to minimize impurities in both nylon and PTFE syringe filters this way.
The membrane choice you make can affect the success and accuracy of your dissolution testing procedures during drug development and quality control. Why not try our filter selector tool to help identify the most appropriate membrane filter for your application? Or, contact GE Healthcare Life Sciences Support for help with any aspect of your dissolution testing process.