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Eur J Pharm Biopharm. 2014 Nov;88(3):807-15. doi: 10.1016/j.ejpb.2014.09.006. Epub 2014 Oct 6.

Development and evaluation of chitosan and chitosan/Kollicoat® Smartseal 30 D film-coated tablets for colon targeting.

Author information

1
Institute of Pharmaceutical Sciences, Dept. of Pharmaceutical Technology and Biopharmacy, Albert Ludwig University, Freiburg, Germany. Electronic address: michaeldrechsler@gmx.de.
2
Physiolution GmbH, Greifswald, Germany. Electronic address: ggarbacz@physiolution.eu.
3
Freiburg Materials Research Center, Albert Ludwig University, Freiburg, Germany. Electronic address: ralf.thomann@fmf.uni-freiburg.de.
4
Institute of Pharmaceutical Sciences, Dept. of Pharmaceutical Technology and Biopharmacy, Albert Ludwig University, Freiburg, Germany; Freiburg Materials Research Center, Albert Ludwig University, Freiburg, Germany. Electronic address: rolf.schubert@pharmazie.uni-freiburg.de.

Abstract

The aim of the present study was to develop film-coated tablets which release a minor amount of the active pharmaceutical ingredient (API) into the stomach and small intestine, yet show a sharp increase of drug release in the colon. Tablets containing the model drug Diclofenac-Na, microcrystalline cellulose as a filler (MT), as well as tablets consisting of Ludiflash® (LT), both were used as tablet cores, respectively. Either chitosan (CHI) alone or different ratios of chitosan and Kollicoat® Smartseal 30 D (KCSS) were applied onto these cores. The resulting film-coated tablets were analyzed for swelling, drug dissolution and stability. In order to clarify whether the colon release is mainly enzyme-driven or pressure-controlled, the coated tablets were both tested in the colon microflora test (CMT), which simulates the enzyme environment within the colon, and using a bio-relevant dissolution apparatus mimicking the intraluminal pressures and stress conditions present in the gastrointestinal tract (GIT). CHI/KCSS (25:75) coated LTs showed a pressure-controlled site-specific drug release in the large intestine, while remaining intact in the upper GIT. CHI as well as CHI/KCSS (25:75) applied onto MTs, remained stable during the entire simulated bio-relevant dissolution transit of the GIT, but showed enzymatically controlled colon targeting in the CMT. These results could be confirmed for CHI/KCSS (25:75) film-coated MTs top-coated with an additional hydroxypropylmethylcellulose (HPMC) layer and an Eudragit L 30 D-55 (EUL) layer to avoid the dissolution in the fasting stomach.

KEYWORDS:

Bio-relevant dissolution; Chitosan; Colon delivery; Colon microflora test; Enzymatic degradation; Film coating; Intraluminal pressure; Kollicoat® Smartseal 30 D

PMID:
25301294
DOI:
10.1016/j.ejpb.2014.09.006
[Indexed for MEDLINE]

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