Using a Non-Compendial Dissolution Apparatus
A common question I receive from dissolution chemists is "when can I use a non-compendial dissolution apparatus?" A non-compendial dissolution apparatus would be any novel dissolution apparatus or modification to existing dissolution systems that is not covered in the USP or other pharmacopeia. Non-compendial dissolution apparatus may be desired for a number of different reasons such as:
-Smaller volume systems for low dose drugs where LOD/LOQ are presenting a challenge
-Large volume systems for drugs with poor solubility or high doses
-Modifications to improve the hydrodynamics of the system
-Modifications to reduce variability or better hold/contain the dosage form
If you'd like to use a non-compendial dissolution apparatus, the first step will usually be to demonstrate the standard apparatuses and accessories will not work for your product. Depending on your specific challenge, the apparatuses you work with and tests needed can be different. For example, if you're having issues with LOD/LOQ, you would first need to demonstrate that you cannot achieve proper analysis at 500mL which is the lowest volume in App 1 and 2. If you believe you need a peak vessel to eliminate coning, you would need to demonstrate that you can't overcome coning at reasonable RPM speeds and/or you get better discriminatory power with a peak vessel.
Once you have established that compendial systems are not adequate for your dosage form, the next step would be to evaluate commercially available systems and modifications for potential solutions. Commercially available is preferred so that the test can be scaled up to multiple dissolution units and labs (including those of the regulatory agencies). Slight modifications to existing dissolution systems are preferable over larger overhauls. Small-volume dissolution vessels, basket over paddle set-ups (pictured above), peak vessels, and more are common changes to systems. Sometimes, these systems will become compendial over time and use such as with the Enhancer cell for testing semi-solids. Some modifications may not appear in a USP chapter - but may show up in a drug monograph (such as the suspended basket over paddle in the Felodipine USP monograph) or as an FDA accepted method (the peak vessel has some accepted methods published).
When you've chosen a non-compendial approach you would like to use, you will need to make sure that the dissolution system is still reproducible and sound through some checks on the system's alignment/performance. This may be done through a modified MQ procedure or some other checks. This would depend quite a bit on what is actually being changed. If there's a specific set-up you're curious about, feel free to comment/message me.
Once you have a system which is aligned as needed, you would then perform testing as needed. A non-compedial system not only has to produce a useful dissolution method, but also demonstrate that the results are better than those you would get from a compendial dissolution apparatus. A dissolution method with a non-compendial set-up must still meet all of the requirements a dissolution method such as discrimination, robustness, accuracy, precision, etc. as well as show that it is a superior set-up.
Non-compendial systems can be incredibly helpful in dealing with a wide variety of challenges presented by new dosage forms. I encourage you to experiment with them as needed, and I'm happy to offer suggestions and advice.
Is it acceptable for Europe filing???
There is a dissolution procedure published by ASTM which was actually written and approved by FDA. Since this is a consensus standard AND was created by the FDA it should not result in additional work on your part or in delays to the submission. Have a look at it and assess whether it works for you. It's ASTM E2503-07
Dear Mr Ken , I would like to read your opinion on my way to see dissolution test "I took a look at the dissolution test processes and I start to compare it to the human digestive system from the moth to the stomach I can’t see big much between the two processes . I believe that the dissolution of the product should exploit the trip from the moth to the stomach, on the other hand, every part should have it part of dissolution and the test should simulate the process of human digestive including strategy to release the final dose in the right place and the right time . Just an opinion ."
An excellent article but be warned-although all your work with a new procedure may be scientifically justified and, in fact, a vast improvement on the current USP/FDA procedure you will potentially cause delay to your application. You will certainly need to do a lot of work including a detailed demonstration why the "official procedures" are not suitable. Unfortunately it is this barrier that is responsible for many companies not investing in new methodologies-simpler to live with poorer methods rather than follow the via dolorosa of change.