Colon-specific delivery of R68070, a new thromboxane synthase inhibitor, using chitosan capsules: Therapeutic effects against 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats

Chitosan, a natural polysaccharide, is being widely used as a pharmaceutical excipient. It is obtained by the partial deacetylation of chitin, the second most abundant natural polymer.Chitosan comprises a series of polymers varying in their degree of deacetylation, molecular weight, viscosity, pKa etc. The presence of a number of amino groups permit chitosan to chemically react with anionic systems, thereby resulting in alteration of physicochemical characteristics of such combinations.Chitosan has found wide applicability in conventional pharmaceutical devices as a potential formulation excipient, some of which include binding, disintegrating and tablet coating properties. The polymer has also been investigated as a potential adjuvant for swellable controlled drug delivery systems. Use of chitosan in novel drug delivery as mucoadhesive, gene and peptide drug administration via the oral route as well as its absorption enhancing effects have been explored by a number of researchers.Chitosan exhibits myriad biological actions, namely hypocholesterolemic, antimicrobial and wound healing properties. Low toxicity coupled with wide applicability makes it a promising candidate not only for the purpose of drug delivery for a host of drug moieties (antiinflammatories, peptides etc.) but also as a biologically active agent.It is the endeavour of the present review to provide an insight into the biological and pharmaceutical profile of chitosan. Various investigations carried out recently are reported, although references to research performed on chitosan prior to the recent reviews have also been included, where appropriate.

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“…Similar results were obtained with the colon specific delivery of R68070, a new thromboxane inhibitor (Tozaki et al 1999b).…”

Section: Colon Targetingsupporting

confidence: 81%

Chitosan: some pharmaceutical and biological aspects - an update

Singla

Chawla

2001

Journal of Pharmacy and Pharmacology

705

363

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“…Thus, systems formulated using ChI as a binder have been found to protect majority of drug release during the usual upper GIT transit time of 5 h. However, there have been a number of reports where ChI has been found to be digested by the microflora of the colon (8,22,23,25). On similar lines, once these matrix tablets reaches the colon, ChI and ChS shall be broken down by the microflora of the colon, and the total amount of drug shall be released from the dosage form.…”

Section: Discussionmentioning

confidence: 99%

Chitosan–Chondroitin Sulfate Based Matrix Tablets for Colon Specific Delivery of Indomethacin

Amrutkar¹,

Gattani²

2009

AAPS PharmSciTech

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Abstract. The different approaches for targeting orally administered drugs to the colon include coating with pH-dependent polymers, design of time-release dosage forms, and the utilization of carriers that are degraded exclusively by colonic bacteria. The aim of the present study was to develop a single unit, sitespecific drug formulation allowing targeted drug release in the colon. Matrix tablets were prepared by wet granulation using cross-linked chitosan (ChI) and chondroitin sulfate (ChS) polysaccharides as binder and carrier. ChS was used to form polyelectrolyte complexes (PEC) with ChI, and its potential as a colon-targeted drug carrier was investigated. Indomethacin was used as a model drug. The ChI and ChS PEC was characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction studies (XRD). The matrix tablets were tested in vitro for their suitability as colon-specific drug delivery systems. FTIR demonstrated that the PEC forms through an electrostatic interaction between the protonated amine (NH 3 + ) group of ChI with the free carboxylate (COO − ) group and sulfate (SO 4 2− ) group of ChS. DSC and XRD indicated that the PEC has different thermal characteristics from ChI or ChS. The dissolution data demonstrates that the dissolution rate of the tablet is dependent upon the concentration of polysaccharide used as binder and matrix and time of cross-linking. The study confirmed that selective delivery of indomethacin to the colon can be achieved using cross-linked ChI and ChS polysaccharides.

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“…In addition, chitosan has been widely applied as a potential formulation excipient in conventional pharmaceutical devices. This polymer also has been investigated as a potential adjuvant for orally controlled release systems [30] and colon targeting [4][5][6][7] . In addition, it was reported that chitosan had mucoadhesive properties, which probably was mediated through ionic interactions with negative charges in mucus or on cell surfaces.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we hope to find some absorption enhancers to augment permeability of rebamipide across the colonic tissues, and in this case, this drug should be specifically localized in the large intestine by its colon-specific delivery to improve its therapeutic effect on colitis and to decrease its side-effects, as well. There are many investigations on absorption enhancers; meanwhile, it has been demonstrated previously that chitosan capsule could act as useful carriers for colon-specific delivery of peptide and anti-inflammatory drugs including insulin, calcitonin, 5-aminosalicylic acid and ridog rel [6][7][8][9] . However, the effects of absorption enhancers increasing the distribution on colon and chitosan capsule on the colonspecific delivery of rebamipide ought to be established.…”

Section: Introductionmentioning

confidence: 99%

Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

Huang¹,

Li²,

Luo³

et al. 2008

WJG

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AIM:To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol significantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10% totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng · h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng · h/mL for chitosan capsule, 1887.9 ng · h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was coadministrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rebamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue significantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifically and the coadministration of C12 with rebamipide may also be very useful in local treatment.© 2008 The WJG Press. All rights reserved.Key words: Rebamipide; Diffusion chamber; Permeability; Sodium laurate; Chitosan capsule; Colon-specific delivery Peer reviewer: Atsushi Nakajima, Professor, Yokohama City University Hospital, 3-9 Fukuura Kanazawaku, Yokohama 236, Japan Huang BB, Li GF, Luo JH, Duan L, Nobuaki K, Akira Y. Permeabilities of rebamipide via the rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier.

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Colon-specific delivery of R68070, a new thromboxane synthase inhibitor, using chitosan capsules: Therapeutic effects against 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats

Cited by 54 publications

References 7 publications

Chitosan: some pharmaceutical and biological aspects - an update

Chitosan: some pharmaceutical and biological aspects - an update

Chitosan–Chondroitin Sulfate Based Matrix Tablets for Colon Specific Delivery of Indomethacin

Permeabilities of rebamipide via rat intestinal membranes and its colon specific delivery using chitosan capsule as a carrier

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