How Do You Choose an RPM in Dissolution?

I’ve seen a couple of “A.I. Slop” articles on LinkedIn this week about how to choose an RPM speed in dissolution, so I thought it might be a good time to re-visit this subject. Agitation speed is one parameter that we can work with in developing a dissolution method. As with every parameter in the dissolution method, we are looking to find a balance between our method to be discriminating and robust. In simple terms, we are looking to choose an optimum speed where the dissolution unit isn’t a blender that breaks everything open by force and not so gentle that the media is stagnant.

The primary goal of agitation in dissolution is to continuously wash fresh media across your dosage form. Imagine that as your product is dissolving that you have a solid particle surrounded by a hazy layer of supersaturated drug in your media. Proper mixing should allow you to wash off this hazy layer so that our dissolution rate isn’t slowed artificially by the supersaturated layer.

RPM speeds depend on the properties of the dosage form. Some products disperse more easily, and some are going to be much more resistant. Method development should be done at multiple RPM speeds in order to find the best fit for your formulation. Reviewing the USP and FDA Dissolution Method databases can be a lot of help here. Some rules of thumb:

25 RPM – Suspensions
50-75 RPM – Most solid oral dosage forms are tested in this range
100 RPM – Typical upper range for solid oral dosage forms

This is usually chosen for products which are gummier/stickier, have coning issues, etc. Choosing an RPM at this range will require you to demonstrate that lower RPMs and other approaches aren’t suitable.

Over 100 RPM – These are infrequently used, and most likely when dealing with products like HPMC capsules, chewable tablets, gummies, etc. Again, this requires a lot of justification.

There are alternate approaches to higher RPMs that may be more discriminating. A dissolution method developer should consider if the Apex vessel, stationary basket over paddle, or USP

Apparatus 3 approach may offer better discrimination at a lower agitation speed.

This is a complex topic – but I hope this gives a good overview on how and why certain RPMs are chosen in dissolution.

Resource Person: Ken Boda