Dissolution is vital in all stages of a product's life, from initial formulation development all the way through to stability testing. Stability testing is key for medicines as it determines their shelf life and storage conditions. Stability testing may also inform us on the need for packaging changes as well. Dissolution is critical in stability, because it is able to tell us the performance of our product over time and under the different stressed conditions. What are some important things to consider and look for when performing dissolution testing of stability samples?
When performing stability testing, you are working with a validated dissolution method. If you fail during stability with your dissolution, then you have failed and it isn't permissible to change the method at this point. The only allowed method modification is the addition of the appropriate enzyme if working with capsules and cross-linking of the gelatin capsule shells is observed. Hopefully, the use of the enzyme has already been validated as well as part of the method validation so that you don't have any surprises. Review USP <711> for more information.
When performing dissolution on stability samples, observations are key in helping determine if there have been changes to the product over time. Cross-linked gelatin is the most dramatic change that is seen, but it isn't the only one. You may also see that the product has a more rigid cone than at previous stability points. You may see the product not disintegrate completely and there are clumps seen. A lot of strange things can happen to your products over time with exposure to light, heat, and humidity.
If you do fail, look at all of the testing done on that sample and see if there is a larger picture about the issue with the product. Dissolution isn't the only test after all. Some things to look out for:
- Assay/CU - lower potency, drug degradation
- Hardness - increased or decreased hardness
- Moisture changes
- Appearance - color changes or changes in the sheen
- Disintegration time longer
Pay attention in trends over your stability pulls as well. You may find that you almost never go to S2 with new lots, but start seeing this happen for frequently as the months on stability go on. This is a leading indicator of stability changes to come.
Make sure the full picture of stability testing is given to management, etc. to determine if changes in packaging, storage conditions, and even labeling on your drugs are needed.
Read also:
- Statistical Analysis Practice in Dissolution Profile Comparison
- The Effects of Storage Condition in Dissolution
Resource Person: Ken Boda (Dissolution Product Specialist at Agilent Technologies)
