Are You Having Dissolution Method Development Challenges? Have You Considered USP Apparatus 3?

(The following article is paraphrased from a previous LinkedIn post by , Agilent’s US Product Specialist for Dissolution.)

The vast majority of dissolutions are performed using USP Apparatus 1 (baskets) and 2 (paddles), but when should you consider USP Apparatus 3?

The Apparatus 3, or Bio-Dis, was initially designed for automated pH changes to mimic the in vivo environment more closely than a single vessel system. The sample is placed in an inner glass tube and agitated by reciprocation a distance of 10cm within an outer glass tube. When the sample is done in a row of media, the inner tube is simply lifted, moved to the next row, and lowered into the next row. Each row can be programmed for different speeds - DPMs or dips per minute - and lengths of time, allowing for greater mimicking of in vivo conditions.

The design of the Apparatus 3 makes it very useful for a wide variety of formulations, including:

  • Media change methods > These are simplified as the unit moves automatically from row-to-row making the App 3 system useful for enteric-coated dosage forms or capsules with time release beads. It is a very useful tool for working with any formulation requiring a pH change, and, in my opinion, essential for any formulations requiring more than a single pH change. By having the system change media and other conditions automatically, you drastically reduce the manual labor required as well as reducing errors that occur with typical pH change processes. The use of Apparatus 3 for these products is well documented.
  • Products that exhibit sticking, coning, or agglomerating beads that can't be overcome with traditional RPMs in USP App 1 or 2 > Products that form dense cones at the bottom of the vessel in an Apparatus 2 method or have agglomerating pellets can be challenging to overcome. If coning still occurs at a relatively high speed (>75 RPM), changes to the system such as using an Apex (Peak) vessel or trying the Apparatus 3 may be necessary. Since the Apparatus 3 uses a dipping motion, there isn’t a point at which the dosage form or it’s disintegrated products can settle. This allows for much greater interaction between the formulation and the media and eliminates the variability that can come from coning issues. Even a moderate dip speed such as 10-15 DPM can overcome common coning challenges.
  • Chewable formulations, veterinary, or difficult to open products > The App 3’s improved shear forces could improve overall dissolution performance. Beads can even be added into the inner tubes to create an abrasive force to simulate food effects and chewing. Chewable formulations such as gums and chewable tablets often require much higher agitation than Apparatus 1 and 2 can provide. The Apparatus 3 offers greater mixing forces than these two systems, and it can also be adapted in 2 ways to increase agitation further. One option is a wider lower cap, which greatly increases the mixing of the system beyond what is found with the USP design. Another option to consider is the addition of inert plastic or glass beads into the inner tube. These beads can act as abrasive agents to help break apart the dosage form as well – and act like teeth or food particles in eroding the dosage form.
  • Gelatin Capsule Shells – Higher shear forces and the ability to change dissolution media can also help with gelatin capsule shells which can cross-link. Cross-linking leads to a shell which is much more resistant to opening due to additional bonds formed, and the increased shear forces of the Apparatus 3 motion can help to break apart shells with mild to moderate cross-linking. In addition, these capsule shells are treated with enzymes to cleave these gelatin molecules to open them. 
    • Note regarding use of enzymes > Enzymes used in a dissolution method may not be compatible with surfactants or may clog HPLC columns. One way to alleviate these challenges is an enzyme pre-soak which is now allowed in the USP. In the enzyme pre-soak, you can perform the dissolution test in media containing enzyme and without surfactant under the same conditions as you would use for the rest of the test, and then move onto the rest of the dissolution method after the pre-soak is performed in a media with surfactant and without the enzymes. The pre-soaking is a perfect fit for the functionality of the Apparatus 3.

USP Apparatus 3 offers flexibility for labs working with challenging formulations or when looking for in vivo in vitro correlations (IVIVC). If you'd like to know more, contact the Agilent team at dissolution.hotline@agilent.com

DE11860579

Anonymous
Was this helpful?