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HERO ID
3013354
Reference Type
Journal Article
Title
Gastrointestinal release behaviour of modified-release drug products: dynamic dissolution testing of mesalazine formulations
Author(s)
Goyanes, A; Hatton, GB; Merchant, HA; Basit, AW
Year
2015
Is Peer Reviewed?
Yes
Journal
International Journal of Pharmaceutics
ISSN:
0378-5173
EISSN:
1873-3476
Volume
484
Issue
1-2
Page Numbers
103-108
Language
English
PMID
25721685
DOI
10.1016/j.ijpharm.2015.02.051
Web of Science Id
WOS:000351317400012
Abstract
The aminosalicylate mesalazine (mesalamine) forms the mainstay of treatment in ulcerative colitis (UC), a disease for which many commercial modified-release products have been developed with the aim of providing targeted gastrointestinal release. The release profiles of five of these commercial formulations were evaluated in bicarbonate buffer using a novel dissolution model that mimics the dynamic conditions of the gastrointestinal tract. Monolithic and multi-particulate mesalazine formulations with pH-dependent and/or independent release mechanisms were evaluated (Asacol(®) 800, Octasa(®), Mezavant(®) XL, Salofalk(®), Pentasa(®)), and each of the products displayed a distinctive dissolution profile. The dissolution results for Mezavant(®) XL (Lialda(®)) (lag time 290 min) demonstrated good correlation with previously reported in vivo disintegration times assessed by gamma-scintigraphy in humans. Octasa(®) showed a similar lag time to Mezavant(®) XL. Drug release from Asacol(®) 800 (Asacol(®) HD) showed a wide standard deviation, reflecting the great variability in vivo. Salofalk(®) displayed both delayed release and extended release characteristics. Pentasa(®) released more than 50% of its drug load in the stomach compartment of the model, which is attributed to the absence of a gastro-resistant coating in this product. The new dissolution method provided a realistic and discriminative in vitro assessment of mesalazine release from different formulations. These results demonstrate that this strategy can be used to predict intestinal release behaviour, and potentially aid the rational design of products developed to target different sites of the gut.
Keywords
5-Aminosalicylic acid; 5-ASA; Colonic delivery; Enteric coatings; Biorelevant dissolution; Physiological bicarbonate buffers
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