This is a recording of a webinar I gave on How To Measure Zeta Potential More Confidently.
I show you how you can maximize the confidence in your measurements - and their interpretation - needed for robust decision making.
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TRANSCRIPT
Let's move on now to the real world. I've mentioned a couple of times the challenges of real-world samples and I'm going to talk about a project that I was asked to get involved with when the project team decided to measure zeta potential. The product is a point four percent weight per volume aqueous suspension of a deworming compound called albendazole. It comes in a 10-milliliter plastic vial and is a single oral dose as opposed to having a reservoir where you meter a known amount of the suspension for delivery. The formulation is highly viscous and sediments very slowly. As a result, it forms a compact sediment. It's important that the patient can resuspend the drug with minimum effort and that it sufficiently disperses to ensure the patient gets the full dose. In 2013 that wasn't an issue. One of the quality control tests used involves a LumiSizer to centrifuge a sample, followed by looking at the appearance of the supernatant and then shaking the sample to assess the redispersibility of the sediment. In 2015, there were product failures. The amount of the drug getting resuspended was low because it wasn't possible to fully redisperse the sediment. You can see the post-sedimentation differences in the top two images. So, what may have changed and what are the important features from a colloid science perspective that may be affecting this behavior?
Let me talk a bit about the sedimentation and redispersion process, and how it can be affected by the zeta potential. If you have a high zeta potential, then it's likely that you will slow any aggregation and as a result you'll get slow settling. This will allow a tight sediment to form that will require considerable energy to redisperse. This is made worse by increasing the viscosity. It's highly probable that you'll leave some of the sediment behind and you will fail your quality control test.
What about low zeta potential? You'll get fast aggregation limited by the diffusion and concentration of the particles. Aggregates that form will settle faster than the individual particles. This will form a loose fluffy sediment and that will readily resuspend. But it doesn't necessarily redisperse to the original primary particles. So, you get the right amount of the material back into the liquid but it's not uniform. For this product, it may not matter as long as the patient can get the entire dose.
I know from experience with a different product that the optimum aggregation state could lie somewhere between these two extremes. How do you make use of the zeta potential data if you want to try and come up with the optimum aggregation state? Do you use a Quality by Design approach? Can you demonstrate that the zeta potential is a critical quality attribute? Can you use the measurement of zeta potential to determine if your manufacturing process or your stability testing is going to fail? To answer that you need to understand the composition of your product. You need to understand the colloid science. And you need to understand why you want to measure the zeta potential.
This is the composition of the product I'm referring to. It has fourteen components. There's one ionic surfactant. There are two nonionic surfactants. There's a polymer. There are five simple ionic compounds. There are two simple nonionic compounds. There are two particulates: the drug itself and a clay to increase viscosity. There are more viscosity modifiers. Not all of the ingredients' structures are known. Elucidating a mechanism in this system that could explain the observation leading to failure and linking that somehow to zeta potential is not going to happen. To measure the zeta potential for something like this by electrophoretic light scattering is a big challenge. It has to be diluted. And there's the clay. It's a lot bigger than the drug and it's got a higher refractive index. So it may dominate the scattered light signal and you may not see a difference in the zeta potential even though the drug particles may be demonstrating some different surface chemistry that would lead to a different zeta potential. It could explain why you're having a problem, but you won't see it because it's swamped by the other particulate material in your product. Diluting can affect surface equilibria...[visit learn.enlighte... for full transcript]
18 сен 2024
