We have located links that may give you full text access.
In vivo evaluation of supersaturation/precipitation/re-dissolution behavior of cinnarizine, a lipophilic weak base, in the gastrointestinal tract: the key process of oral absorption.
European Journal of Pharmaceutical Sciences 2017 January 2
The aim of this study is to evaluate how supersaturation, precipitation, and re-dissolution processes influence the intestinal absorption of cinnarizine (CNZ), a lipophilic weak base, by monitoring its plasma and luminal concentration-time profile, after oral administration as a HCl solution containing fluorescein isothiocyanate dextran (FD-4), a non-absorbable marker. In the in vitro pH shift experiment, the supersaturation stability was significantly lower when the higher-concentration solution of CNZ (pH1.5) was added to the simulated intestinal fluid. However, although the in vivo bioavailability after oral administration of high and low dose as HCl solutions was greatly improved compared to those as neutral suspensions, the difference in the supersaturation stability was not reflected in the improvement of the in vivo bioavailability. Analysis of CNZ and FD-4 concentrations in each segment of the gastrointestinal tract revealed that most of the CNZ precipitated in the duodenum after gastric emptying, and supersaturation was observed only in the duodenum. Thereafter, the precipitate was rapidly re-dissolved and absorbed in the upper and middle small intestine. The rapid re-dissolution may be caused by smaller particles of the precipitate. In this case, it is considered that the key process for the absorption of CNZ was re-dissolution, not supersaturation. Therefore, different supersaturation stabilities in different doses observed in in vitro precipitation experiment was not reflected to in vivo absorption. These findings may be useful to design efficient supersaturable formulations and to validate and improve current prediction methods.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app