Vieira, ACF;
Serra, AC;
Veiga, FJ;
d’A Rocha Gonsalves, AM;
Basit, AW;
Murdan, S;
(2016)
Diclofenac-β-cyclodextrin for colonic drug targeting: in vivo performance in rats.
International Journal of Pharmaceutics
, 500
(1-2)
pp. 366-370.
10.1016/j.ijpharm.2016.01.024.
Preview |
Text
Murdan_Final Revised Murdan et al text_final after proofs.pdf Download (528kB) | Preview |
Abstract
The aim of this in vivo study was to assess the ability of the prodrug conjugate diclofenac-β-cyclodextrin to release diclofenac in the colon following oral administration, using sulfapyridine (a metabolite of sulfasalazine) as a marker of colonic absorption. Two groups of rats were used; the test rats received a suspension containing the two prodrugs, diclofenac-β-cyclodextrin and sulfasalazine, while the control rats received a suspension containing the corresponding free drugs, sodium diclofenac and sulfapyridine. The rats were fasted overnight with free access to water before and throughout the first 12 hours of the study. Blood was collected from the tail vein at pre-determined time points and the plasma analyzed for the concentrations of diclofenac and sulfapyridine. Following the oral administration of the two prodrugs, a more extended absorption profile was observed and Cmax was achieved 10 hours post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3 h, and that of sulfapyridine being 2.1 h) . In addition to a later tmax, conjugation of diclofenac to β-cyclodextrin also resulted in a reduced Cmax and a reduced AUC. The same tmax for diclofenac-β-cyclodextrin as for sulfasalazine confirms the colonic metabolism of diclofenac-β-cyclodextrin. This study shows the potential of this new cyclodextrin-based prodrug to target and release diclofenac specifically in the colon following oral administration.
| Type: | Article |
|---|---|
| Title: | Diclofenac-β-cyclodextrin for colonic drug targeting: in vivo performance in rats |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ijpharm.2016.01.024 |
| Publisher version: | http://dx.doi.org/10.1016/j.ijpharm.2016.01.024 |
| Language: | English |
| Additional information: | © 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0. |
| Keywords: | large intestine, colonic targeting, microbiota, gut, conjugate, cyclodextrin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1474059 |
Archive Staff Only
 |
View Item |
