Utility of gastric‐retained alginate gels to modulate pharmacokinetic profiles in rats. Issue 8 (6th June 2013)

• Record Type: Journal Article
• Authors: Foster, Kimberly A.; Sun, Huadong; Fancher, Roderick Marcus; Proszynski, Mirek; Dixon, George; Ford, Kenneth; Cornelius, Georgia; Gudmundsson, Olafur S.; Hageman, Michael J.
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 8(2013:Aug.)
• Page Start: 2440
• Page End: 2449
• Publication Date: 2013-06-06
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23630
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A gastric‐retentive formulation amenable to dosing in rodents has the potential to enable sustained release in a preclinical setting. This may be useful to provide systemic exposure over a longer duration or to increase duration of exposure for compounds with targets localized in the gastrointestinal tract. Previous work has shown that a mixture of 1% sodium alginate and 0.625% karaya gum in the presence of a calcium chelator can form gels <italic>in situ</italic> that are gastric retained in rats. The aim of this work was to define the physicochemical boundaries of compounds within this technology and their relation to <italic>in vivo</italic> release using a series of model compounds with high permeability but varying solubility. <italic>In vitro</italic> data demonstrated a good correlation between solubility and initial release rates from the gels. <italic>In vivo</italic> studies were conducted in Sprague–Dawley rats to compare the exposure profile of compounds dosed in gel relative to a standard formulation. <italic>In vivo</italic> data were consistent with trends from the <italic>in vitro</italic> studies. These data suggest that, in conjunction with an understanding of compound solubility, sodium alginate/karaya gum gels may be a useful tool to modulate exposure profiles in rodent models in a preclinical setting. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2440–2449, 2013</p> </abstract>