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Hi
We have developed buccal liquid formulation, with strength of 10mg/mL. We conducted a PK study, where the drug was administered via the buccal cavity (after instilling the drug between the cheek and gum, the cheek was briefly massaged to facilitate absorption). We have successfully defined Tmax, Cmax, AUC etc. Our clinical colleagues now tell us that they would like us to formulate a higher strength of 20mg/L so that actual administration volume is lower.
My question is, if we double the strength, would you expect an enhanced absorption rate (hence reduced Tmax, increased Cmax)? Does Ficks law rule here? The compound undergoes passive diffusion and is not a transporter substrate.
Regards
Dr Marie Harvey
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It depends on the physico-chemical properties of the molecule and if there is any enhancement by the formulation components/excipients. Some do and some do not, you just have to try it in the absence of those information. The question becomes how important is this reformulation/re-examination to the goals of your project. Will this provide you with the proof of concept that you need and can this be addressed at a later stage in a different clinical setting by adding an arm.
-- Sanjeev Thohan, PhD
SARx Consulting
SARxconsult.aaa.Gmail.com
http://www.linkedin.com/in/sanjeevthohan
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The following message was posted to: PharmPK
Marie,
Do you think or have data that massaging the cheek has any effect?
When exploring the transmucosal route on myself I found that the best
place to put a liquid formulation was under the tongue where volumes
of 1-2ml disappeared rapidly, giving me some confidence that in
patients it would be absorbed before an involuntary swallowing reflex
diverted some of the dose. My impression was that it would be
increasingly difficult to avoid swallowing after 2ml. I wonder if
anyone has compared absorption from the buccal and sublingual areas.
We obtained clear evidence that absorption for a CNS-active compound
was far more rapid, efficient and consistent than the oral route.
Andrew
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The following message was posted to: PharmPK
I will be surprised to see 1-2 ml disappearing from sublingual space. I suspect salivary flush also in that case. Mucosa is thinner in sublingual area compared to buccal and highly vascular giving rise to rapid absorption. However, this is good for potent drugs.
Regards,Ayyappa Chaturvedula
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