• Journal of Pharmaceutical Investigation
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• v.22 no.4
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• pp.251-266
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• 1992

A major problem with the peptide-based drugs is that these drugs must generally be administered by injection. Therefore, there is considerable research interest in alternative routes of delivery, such as buccal, nasal, gastrointestinal route and etc. Site-specific drug delivery to the colon, as an alternative to parenteral drug delivery, is of interest for the delivery of peptide-based drugs as well as the delivery of low molecular weight drugs for the treatment of colonic disease, This review describes some considerations of colon-specific drug delivery using hydrogels.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.964-968
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• 2002

Colon drug delivery is advantageous in the treatment of colonic disease and oral delivery of drugs unstable or suceptible to enzymatic degradation in upper GI tract. In this study, multilayer coated system that is resistant to gastric and small intestinal conditions but can be easily degraded by colonic bacterial enzymes was designed to achieve effective colon delivery of prednisolone. Variously coated tablets containing prednisolone were fabricated using chitosan and cellulose acetate phthalate (CAP) as coating materials. Release aspects of prednisolone in simulated gastrointestinal fluid and rat colonic extracts (CERM) were investigated. Also, colonic bacterial degradation study of chitosan was performed in CERM. From these results, a three layer (CAP/Chitosan/CAP) coated system exhibited gastric and small intestinal resistance to the release of prednisolone in vitro most effectively. The rapid increase of prednisolone in CERM was revealed as due to the degradation of the chitosan membrane by bacterial enzymes. The designed system could be used potentially used as a carrier for colon delivery of prednisolone by regulating drug release in stomach and the small intestine.

• KSBB Journal
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• v.18 no.2
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• pp.161-164
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• 2003

Oral drug delivery system using pectin gel was developed for colon-targeting of peptide drug. BSA(bovine serum albumin)-loaded pectin and pectin-alginate beads were prepared for drug release properties in vitro. Morphological studies by electron microscopy indicated that pectin and pectin-alginate beads were spherical in shape and approximately 1.0 mm. In order to find the suitable beads, effects of cross-linking agents (calcium chloride or zinc acetate) and drying temperature of beads were investigated. Drug release decreased with concentration of cross-linking agents and drying temperature. For colonic drug delivery from pectin and pectin-alginate beads, pectin degradable enzymes were added at 5 hrs from the beginning of drug release. After addition of enzymes, drug release was suddenly increased against free enzymes. Therefore, pectin and pectin-alginate beads can be promised as useful drug release carriers for colon-targeted delivery.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.3
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• pp.191-195
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• 2004

Drug delivery systems that are based on pectin have been studied for colon specific delivery using the specific activity of colon microflora. The aim of this study was to design a novel method of manufacturing pectin microspheres without oils and surfactants and to investigate the potential use of the pectin microspheres as an oral colon-specific drug carrier. The pectin microspheres were successfully formed using the spray drying method and crosslinking with calcium chloride. From the crosslinked pectin microspheres, indomethacin (IND) release was more suppressed than its release from non-crosslinked microspheres. In a low pH (pH 1.4) environment, the pectin microspheres released IND at an amount of about 18${\pm}$2% of the total loaded weight for 24 h while the release rate of IND was stimulated at neutral pH (pH 7.4). IND release from the pectin microspheres was increased by the addition of pectinase. The results clearly demonstrate that the pectin microspheres that were prepared by the spray drying and crosslinking methods are potential carriers for colon-specific drug deliveries.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.232.2-232.2
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• 2002

Corticosteroids have been used most frequently for inflammatory bowel disease. They are well absorbed and only a limited fraction of the dose is delivered to the inflammatory site in the colon. To reduce side effects by the systemic absorption. colon-specific delivery is highly desirable. We designed dexamethasone 21-sulfate sodium (DS) as a cOlon-specific prodrug of dexamethasone (D) expecting that it might be stable and non absorbable in the upper intestine and dissociate in the colon by the sulfatase, an enzyme solely found in the colon. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.177.3-177.3
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• 2003

Corticosteroids have been used most frequently for inflammatory bowel disease. To reduce side effects by the systemic absorption, colon-specific delivery is highly desirable. We expected that conversion of 21-hydroxyl in glucocorticoids into a sulfate ester sodium will greatly increase the hydrophilicity, which consequently restrict the gastrointestinal absorption. Once delivered to the colon, sulfate ester will be hydrolyzed by the sulfatase originated from microbes and release the parent compound, glucocorticoids. In this study, we prepared methylprednisolone 21-sulfate sodium (MPS) and investigated its suitability as a colon-specific prodrug on methylprednisolone (MP). (omitted)

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.258-263
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• 2003

Colon-specific delivery of glucocorticoids is highly desirable for the efficient treatment of inflammatory bowel disease. We synthesized prednisolone 21-sulfate sodium (PDS) as a colon-specific prodrug of prednisolone (PD) and investigated its properties using rats as test animals. We expected that introduction of sulfate ester as a sodium salt might increase the hydrophilicity and restrict the absorption in the GI tract. If PDS is stable and nonabsorbable in the upper intestine, it will be delivered to the colon as an intact form, where it hydrolyze by the sulfatase to release PD. Compared with PD, the solubility of PDS increased and the apparent partition coefficient decreased greatly. PDS was stable on incubation with pH 1.2 and 6.8 buffer solutions and with the contents of the stomach and small intestine. On incubation with the cecal contents, PDS decreased to 9.6％ of the dose in 10 h producing PD. The amount of PD increased to give a maximum 54％ of the dose and decreased. As a control, when PD was incubated with the cecal contents, it decreased to 29％ of the dose in 8 h, which implied that reduction of PD proceeded under such conditions. These results suggested that hydrolysis of PDS took place to produce and accumulate PD, which decreased by reduction as the incubation period extended. Our results suggested that PDS can be a promising colon-specific prodrug of PD, and sulfate ester group might serve as a potential colon-specific promoiety, especially for the drugs which are resistant to reduction in the colon.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.264-269
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• 2003

5-Aminosalicylic acid (5-ASA) is an active ingredient of therapeutic agents used for Crohn s disease and ulcerative colitis. Because it is absorbed rapidly and extensively in the upper intestine, delivery of the agent specifically to the colon is necessary. We selected taurine as a colon-specific promoiety and designed 5-aminosalicyltaurine (5-ASA-Tau) as a new colon-specific prodrug of 5-aminosalicylic acid (5-ASA). It was expected that introduction of taurine would restrict the absorption of the prodrug and show additive effect to the anti-inflammatory action of 5-ASA after hydrolysis. 5-ASA-Tau was prepared in good yield by a simple synthetic route. The apparent partition coefficient of 5-ASA-Tau in 1-octanol/pH 6.8 phosphate buffer or $CHCl_3$/pH 6.8 phosphate buffer was 0.10 or 0.18, respectively, at $37^{\circ}C$. To determine the chemical and biochemical stability in the upper intestinal environment, 5-ASA-Tau was incubated in pH 1.2 and 6.8 buffer solutions, and with the homogenates of tissue and contents of stomach or small intestine of rats at $37^{\circ}C$. 5-ASA was not detected from any of the incubation medium with no change in the concentration of 5-ASA-Tau. On incubation of 5-ASA-Tau with the cecal and colonic contents of rats, the fraction of the dose released as 5-ASA was 45% and 20%, respectively, in 8 h. Considering low partition coefficient and stability in the upper intestine, 5-ASA-Tau might be nonabsorbable and stable in the upper intestine. After oral administration, it would be delivered to the colon in intact form and release 5-ASA and taurine. These results suggested 5-ASA-Tau as a promising colon-specific prodrug of 5-ASA.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.248.1-248.1
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• 2003

Glucocorticoids are used most widely for the treatment of inflammatory bowel disease (IBD). For the efficient treatment and reduction of side effects, colon-specific delivery of a glucocorticoid is highly desirable. Previously, we synthesized prednisolone 21-sulfate sodium (PDS) as a colon-specific prod rug of prednisolone (PD) expecting that it might be stable and nonabsorbable in the upper intestine and hydrolyze in the colon to release PD. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.357.2-357.2
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• 2002

Corticosteroids have been used most frequently for inflammatory bowel disease.They are well absorbed and only a limited fraction of the dose is delivered to the inflammatory site in the colon. To reduce side effects by the systemic absorption. cOlon-specific delivery is highly desirable. We prepared prednisolone 21-sulfate sodium (PDS) and investigated its suitability as a colon-specific prodrug of prednisolone(PD). (omitted)