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The Effect of Sampling Cannula on In Vitro Dissolution Testing

A recent issue of the AAPS Journal has published a research paper from the FDA regarding the effects of sampling cannula on In Vitro dissolution testing when using a USP Apparatus 2 (Paddle) method.

Testing a range of sampling cannula OD's, being used with both static and intermittent sampling procedures, the report dispels a couple of common misconceptions surrounding these factors.

You can read the full publication here, but the main conclusions from the FDA's research are as follows:

  • The Outer Diameter (OD) of the sampling cannula had a significant effect on the dissolution release rate of the test product. Cannulae with a small OD have a negligible effect on release rate, whereas cannulae with larger OD's increase the release rate substantially. The authors conclude: The degree of interfer- ence on dissolution results is directly related to the size of the sampling cannula. Large sampling cannulas (OD > 6 mm) are shown to cause significant changes (p < 0.05) due to severe hydrodynamic disturbances in the dissolution results of tested 10 mg prednisone tablets. Using smaller sampling cannulas (OD < 3.6 mm) may be required to minimize error in dissolu- tion results, especially for drug products that are sensitive to medium hydrodynamics.

  • The addition of a filter tip increases the above impact further still, with the authors noting: 'Because a filter tip may dramatically increase the OD of sampling cannula, the sampling procedure requiring a filter at the end of each sampling cannula should be avoided.'

  • Intermittent sampling (whereby the cannulae are placed into the dissolution media for sampling then withdrawn again at each timepoint) has a dramatic increase on the variability of the test result. This intermittent sampling technique is commonly utilised by several dissolution tester manufacturers via the use of an automatic sampling manifold. The authors note: 'Sampling cannulas in the intermittent setting may introduce large variability in dissolution results compared to those in the stationary setting. Current practices that purposely apply intermittent sampling cannula setting to avoid hydrodynamic disturbances may need to be reconsidered.'

Given the above, the paper provides advice regarding the definition of sampling practices on dissolution testing SOP's and methods, citing: 'It is recommended that details on sampling cannula should be documented in the standard operating procedure (SOP) for dissolution testing during method development. The study results also provide a helpful point to consider for in vitro dissolution testing when experimental design requires placing foreign bodies (cannula, thermometer, pH sensor, UV probe, etc.) in the test vessel.'

If you are affected by any of these findings, Omicron are able to guide you through, and supply you with, a range of solutions to help you improve your sampling procedures:

  • We can supply a wide range of sampling cannulae with a sampling shaft OD of 1.6mm.

  • We can supply a wide range of sampling cannulae that use a filter disk held in the probe housing, not on the tip of the cannula.

  • We can supply specialist sampling cannulae that can accommodate a tip style filter in the probe housing, to allow you to circumvent the validation of a new filter type.

  • We can supply vessel covers with sampling ports to enable you to perform static sampling.

  • Our Dissolution testers and auto samplers utilise static, 1.6mm OD sampling cannulae with disk or syringe filters.

If you would like more information on our solutions, or just some helpful advice on how you can make improvements to your current sampling processes, please do not hesitate to contact us


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