The following is a response to a question on LinkedIn Forum, which, I thought, would be valuable to the visitors of this blog as well. I hope you will find it useful. Saeed
Question:
Saeed: Aside from the fact that cGMP is commonly understood as the current norms of industry, would you advise on how your approach would apply to other dosage forms? The maceration/muddling/contact mixing apparatus you’ve designed might be able to replace paddles and baskets for tablets. What would be the solution for testing of sublingual and transdermal films using paddle over disk or cylinders? If you feel that performance verification is necessary (running a “standard” product), wouldn’t you provide a better service to industry by developing a better “standard” product than the Prednisone PVT tablets?
My response:
Louis: Excellent questions. I personally believe that dissolution testing is, and should be, for oral products only. The dissolution tests mimic volume/space, liquid, stirring/mixing, and temperature of the GI tract, in particular intestinal. Other than stirring/mixing environment these apparatuses (paddle/basket) are fine. As the paddle/basket do not provide appropriate stirring/mixing but stagnation, and also highly variable results because of variable settling positions of tablets/capsules at the bottom vessel, they do not mimic GI environment appropriately, thus are not suitable for dissolution testing. Crescent shape spindle addresses these flaws therefore offer better mimicking of GI tract and thus dissolution testing. The reason I explained this is that there is science and logical thinking behind the development and suggestion of the crescent shape spindle. It is not like that OK if paddle/basket does not provide expected results try something else without looking and addressing the cause of the problem.
With this background, my view about sublingual products is that you may try and it might work. As I do not have experience working with such products I can only envision that the crescent shape spindle might provide faster dissolution results than what one would observe in vivo as in in vivo tablets move slower than in vitro with the crescent shape spindle. But then one should be able to conduct dissolution at a lower rpm say 5 for such products. Certainly, you should try.
Concerning patches or other dermal/topical products, I do not think that dissolution testers (paddle/basket or crescent shape spindle) should be used at all. There is no link or simulation of in vivo environment here for such products i.e. science does not support such testing. However, if one insists on using it for some reason, then one may use the same setup for patches with disk and hang it in the vessel from the lid of the vessel or tie it to the rod of the spindle. Most likely results will be better than using paddle/basket as crescent shape spindle provides much better mixing environment.
Concerning developing “standard” tablets, I would not develop standard tablets, like PVT which in my view was a wrong concept. Tablets do not, and cannot, reflect deficiencies of the individual physical parameters of testers and/or tests. The “standard” tablets are only be used to show that, AFTER meeting all the physical specifications collectvely, the tester is “performing” well, i.e. capable of providing expected dissolution results of a PRODUCT for human use (not just any tablets or product). Therefore, I have some ideas of picking up a product, as a “standard” in this regard. I am looking for a product manufacturer who would be interested in working with me for the selection of such a product. So, anyone interested in such (lucrative) work or market, please contact me. I believe it would be a small and short project with big financial reward and service to pharmaceutical industry.
I hope I have answered your questions adequately. Let me know if you require further details.
