In response to a query, I have provided the following opinion on the above-mentioned topic. I thought this topic might have general interest, thus posting it on the blog as well. Comments/critiques are always appreciated.
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Thanks for your interest in my work and the website.
Concerning your question regarding the dissolution test for Nicotine Polacrilex Lozenges, I must say that I have not worked with such products. Therefore, consider my advice as a theory (quick thoughts) that may be workable with some experimental work.
You stated that the release of drugs (nicotine) from the lozenges occurs in 30 minutes in humans. However, in vitro test requires 8 hours for the release. Obviously, somewhere, there is a mismatch between in vitro and in vivo environments. Considering that there is a higher pH (6.2 to 7.4) in the oral cavity than in the intestinal tract, the suggested use of a higher pH of 7.4 for dissolution appears appropriate. My preference would be around 6.0
To me, however, there appear to be two issues here. First, there may be a lack of needed stirring and mixing within the dissolution vessel. I am of the view that the use of the basket/paddle apparatus would be the least efficient choice here. Nicotine Polacrilex is an ion-exchange complex, thus it may require some modest “shake” to pull the drug out of the polymer. Thus, it may require a different mechanism of stirring, may be a crescent-shape spindle as I have proposed, or something of that nature that should be good and efficient in moving the medium from the surface and providing mobility to the lozenges.
The second aspect is related to chemistry. The complex between nicotine and Polacrilex is ionic. Thus, you may need some form of competitive cation in the medium, which would facilitate the pull-out or replacement of nicotine from the ion exchange. Otherwise, ion exchange may keep the nicotine from releasing, which would result in an extra ordinary delay in release (8h?). It is to be noted that working at pH 7.4 (dissolution) is not very favorable to this dissociation, as the pKa of nicotine is 8.5. Having said that, please keep in mind that if you are going to try a competitive cation, this has to be a bio-relevant one. Otherwise, your dissolution test will lose bio-relevancy. Perhaps, CTAB may be tried, a commonly suggested solubilizer (surfactant) for dissolution testing.
Hope this will help.