Dissolution of Chewable Tablets

Chewable tablets and other chewable formulations are increasingly being chosen to reach children and elderly patients. They offer easier swallowing and patient compliance, but they can also make dissolution more challenging. The matrix of chewable formulations tend to be more resistant to dissolution, with gummy and sticky excipients leading to coning and other challenges. While it may be tempting to grind the tablet pre-dissolution to simulate the chewing process, this isn't an allowable approach as you will have patients who swallow these products whole and it must be accounted for. While standard USP Apparatus 1 and 2 may work for some of these products, others will require either modified systems or USP Apparatus 3 to achieve adequate mixing to properly mimic the in vivo environment and show appropriate dissolution.

Most dissolution method development for solid oral dosage forms will begin with Apparatus 1 and 2, and this is also true for chewable products. Before moving to some of the options I lay out below, I would recommend attempting Apparatus 1 and 2 in the 75-100 RPM range first. This may work for your product and provide an easier path forward for testing and regulatory acceptance, and if it doesn't work - it provides the proof you need to show an alternate approach is preferred.

If you find that Apparatus 1 and 2 aren't working and you need an option with greater agitation, then there are a few good options to work with for testing these products. Two of them are simple adaptations of an Apparatus 2 set-up, and the other is USP Apparatus 3 (Bio-Dis).

Apparatus 2 Modifications:

The easiest approach for most labs to test chewable products is to adapt a system that they already have with different accessories that allow stronger mixing or flow across the product.

One option is a Peak vessel. A Peak vessel is a modified version of a standard 1L vessel where the bottom of the vessel had a bump raised at the bottom. This bump replaces the poorly stirred area in the vessel, and can help increase mixing in the off-center location where the tablet would be sitting. The Peak vessel is used in formulations where coning is an issue, and has been shown to offer better discrimination of products at a lower RPM than a standard paddle apparatus. There have been some methods approved by the FDA using these vessels.

Another modification of the USP Apparatus 1 and 2 that could work for a chewable product is a stationary basket over paddle approach. In this configuration, a basket is suspended from the evaporation cover and sits 1 cm above the paddle blade. This option allows much stronger flow across the dosage form than the standard Apparatus 2. This set-up has been used for formulations requiring higher shear forces to break apart, and has been discussed as a potential option to help with gelatin capsules to better deal with cross-linking. There are a couple types of baskets available for use in this configuration. One is an 8-mesh diamond-shaped basket which you can find in the USP monograph for Felodipine. The other option would be a standard basket available in various meshes (I would recommend 10 or 20 mesh), and you can see a photo below.

These 2 options provide relatively easy configuration changes from a standard dissolution system, and with very little additional investment.

Apparatus 3 (Bio-Dis):

Another option for chewable products is the USP Apparatus 3, also known as the Bio-Dis. This system has a different mixing approach, which allows for stronger mixing of the product and greater shear forces. In this system, the inner tube with the dosage form will reciprocate up and down in a 10 cm stroke. The speed is programmable, just as with an Apparatus 1 or 2 system. In addition, this system has multiple testing rows which also enables you to test multiple pHs of media unattended in a single run.

When the Apparatus 3 is working well for a product, it allows for free flow of the formulation within the media and you don't see the product agglomerating as you would tend to see in a basket or paddle system.

The free flow of particles or dosage form within the tube offers a greater potential for break down of a chewable product. In addition, you can also add inert glass or plastic beads in with your formulation - and these would add an abrasive force to the dissolution as well to further assist in the dissolution.

If this agitation isn't enough, you can also slightly modify the Apparatus 3 inner tubes with a wider lower cap. This wider lower cap causes much more force to be directed through the inner tube on the down stroke and can help drive even greater mixing and shear forces. Below is a photo showing the increase in the forces. A powder was placed at the bottom of the vessels (this is not a typical use, just for illustration purposes), and you can see the change in mixing.

Chewable products can be tricky to work with, but these three options can provide a lot of help in dealing with the challenges they can present.

If there are any other dissolution topics you'd be interested in, I'd be happy to help. As always, these short pieces are my personal opinions and don't necessarily reflect my company's position.

Thanks!