title: Development and evaluation of chitosan and chitosan/Kollicoat® Smartseal 30 D film-coated tablets for colon targeting.
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.
authors.affiliation: Institute of Pharmaceutical Sciences, Dept. of Pharmaceutical Technology and Biopharmacy, Albert Ludwig University, Freiburg, Germany. Electronic address: michaeldrechsler@gmx.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Drechsler
authors.affiliation: Physiolution GmbH, Greifswald, Germany. Electronic address: ggarbacz@physiolution.eu.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Garbacz
authors.affiliation: Freiburg Materials Research Center, Albert Ludwig University, Freiburg, Germany. Electronic address: ralf.thomann@fmf.uni-freiburg.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Thomann
authors.affiliation: 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.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schubert
mesh_terms: D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D011145:Polyvinyls / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D013608:Tablets, Enteric-Coated
chemical_list: C477852:Eudragit L 30 D-55; D008689:Methacrylates; D011108:Polymers; D011145:Polyvinyls; D013608:Tablets, Enteric-Coated; C013215:polyvinyl acetate; D048271:Chitosan
keywords: Bio-relevant dissolution; Chitosan; Colon delivery; Colon microflora test; Enzymatic degradation; Film coating; Intraluminal pressure; Kollicoat® Smartseal 30 D