No 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 12h 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 10h post-dose, in contrast to rapid absorption of the free drugs (tmax of diclofenac being 1.3h, and that of sulfapyridine being 2.1h). 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.

Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-rmbeta-cyclodextrin, Carbohydrate Polymers (2014), http://dx.doi.org/10. 1016/j.carbpol.2014.06.064 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and ii) metabolism of two colonic prodrugs, diclofenac-β-cyclodextrin and a commercially 26 available control, sulfasalazine, within the caecal and colonic contents. Male Wistar rats were 27 subject to four different feeding regimens, the gut contents characterized (mass and pH) and 28 the metabolism of prodrugs investigated. 29The feeding regimen affects gut contents (mass and pH), more specifically in the stomach 30 and lower intestine, and affects the rate of metabolism of diclofenac-β-cyclodextrin, but not 31 that of sulfasalazine. The latter's degradation is much faster than that of diclofenac-β-