Dissolution testing provides critical drug release information about solid dosage forms, essential for pharmaceutical quality control and drug development. Filtration has a key role in the process to improve throughput and reduce result variability. Get grounded with this quick overview.
What is dissolution testing?
Drug dissolution testing is a routine test used in the pharmaceutical industry to evaluate the rate of release of an active pharmaceutical ingredient (API) from its dosage form.
This information is essential for pharmaceutical quality control (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 developing release profiles of different formulations. Dissolution testing procedures are detailed in the US Pharmacopeia and the European Pharmacopeia (Ph. Eur), and are required by regulatory authorities.
The test involves several key steps:
- Dissolution of a solid dosage form under controlled conditions in a dissolution vessel.
- Sample 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.
Why is filtration important in dissolution testing?
The aim of drug dissolution testing is to determine the amount of API dissolved at chosen time points as samples are withdrawn from the dissolution vessel. Filtration is key, 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 not only affect the analysis, but may also cause damage and potential clogging to 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.
Key considerations when choosing a filter for dissolution testing
Evaluating potential filter membranes during method validation can help you 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?
- Does the membrane show low analyte binding so good drug recovery is possible?
- Does the membrane show a low level of extractables, to avoid introducing impurities into the sample?
For HPLC analyses, chemical compatibility and low levels of extractables are always important considerations for reducing the risk of new contaminants interfering with results, and for ensuring the membrane filter is well-matched with the solvents and the APIs being investigated.
You will also want to be sure the filter format is suitable for your testing workflows and equipment. Syringe filters are widely used for sample preparation in dissolution testing, as they save time and waste in the lab. If you are using automation in your testing process, there are syringe filters available to work with specific automated systems.
Filter selection influences the accuracy and reliability of dissolution data. An initial validation identifies the various influencing factors, helping to select the most appropriate filter based on the properties of the API and dissolution media.
For a deep dive into the key filter characteristics that influence filter selection, and filter options that are suitable for dissolution testing, read our article, Filter selection for dissolution testing.
By automating all or part of the dissolution test workflow, testing labs can benefit from improved accuracy, precision, and productivity. Learn more in our article about automated dissolution testing methods.
Try our Whatman™ Filter Selector App to find out if you are using the most appropriate filtration solution for your samples. To discuss any challenges you are facing in dissolution testing, please contact Cytiva Scientific Support.