Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Dec 21:11:45-57.
doi: 10.2147/DDDT.S123412. eCollection 2017.

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

Min Soo Kim  1 , Dong Woo Yeom  1 , Sung Rae Kim  1 , Ho Yub Yoon  1 , Chang Hyun Kim  1 , Ho Yong Son  1 , Jin Han Kim  1 , Sangkil Lee  2 , Young Wook Choi  1
Affiliations

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

Min Soo Kim et al. Drug Des Devel Ther. .

Abstract

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD.

Keywords: acidification; chitosan; colon-specific delivery; controlled release; factorial design; microflora.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Stepwise illustration of DL-CDDS as a platform for colon targeting. Notes: (A) In the stomach, the outermost enteric coating layer inhibits drug release; (B) in the small intestine, the inner CTN-dispersed polymeric subcoating layer impedes drug release; (C) in the colon, water infiltrates the core tablet and dissolves CA, resulting in microclimate acidification and pore generation to some extent; (D) in the latter part of the colon, under the influence of microflora, such as CTNase, a number of microporous channels are formed by enzymatic CTN digestion, thus facilitating drug release. Abbreviations: DL-CDDS, double layer-coated colon-specific drug delivery system; CTN, chitosan; CTNase, chitosanase.
Figure 2
Figure 2
Dissolution characteristics of various formulations. Notes: (A) Effect of amount of enteric coating; (B) effect of amount of CTN/EE subcoating; (C) effect of amount of CA in core tablet and presence of CTNase in SCF. Error bars denote standard deviation (n=3). Abbreviations: CA, citric acid; CTN, chitosan; CTNase, chitosanase; EE, Eudragit E100; LXP, loxoprofen sodium; SCF, simulated colonic fluid; SGF, simulated gastric fluid; SIF, simulated intestinal fluid; CA0, citric acid-free tablet; CA15, CA 15 mg; CA30, CA 30 mg.
Figure 3
Figure 3
Comparison for dissolution efficiency of various formulations. Notes: *P<0.05. Error bars denote standard deviation (n=3). Abbreviations: CA, citric acid; CTN, chitosan; CTNase, chitosanase; DE, dissolution efficiency; DEcolon, DE in the colon; EE, Eudragit E100; SCF, simulated colonic fluid; CA0, citric acid-free tablet; CA15, CA 15 mg; CA30, CA 30 mg.
Figure 4
Figure 4
Normal probability plots of the standardized residual (A) and Pareto charts of the standardized effect (B). Notes: X1, polymer composition; X2, amount of subcoating; Y1, dissolution efficiency in simulated colonic fluid; Y2, dissolution efficiency in chitosanase-supplemented simulated colonic fluid; Y3, controlled-release duration in the colon.
Figure 5
Figure 5
Main effect plot (A) and interaction plot (B). Notes: X1, polymer composition; X2, amount of subcoating; Y1, dissolution efficiency in simulated colonic fluid; Y2, dissolution efficiency in chitosanase-supplemented simulated colonic fluid; Y3, controlled-release duration in the colon.
Figure 6
Figure 6
Dissolution profile of the optimized DL-CDDS. Note: Error bars denote standard deviation (n=3). Abbreviations: CTNase, chitosanase; DL-CDDS, double layer-coated colon-specific drug delivery system; LXP, loxoprofen sodium; SCF, simulated colonic fluid; SGF, simulated gastric fluid; SIF, simulated intestinal fluid.
See this image and copyright information in PMC

References

    1. Sinha VR, Kumria R. Polysaccharides in colon-specific drug delivery. Int J Pharm. 2001;224(1–2):19–38. - PubMed
    1. Pawar PK, Gautam C. Design, optimization and evaluation of mesalamine matrix tablet for colon drug delivery system. J Pharm Invest. 2016;46(1):67–78.
    1. Steed KP, Hooper G, Monti N, Benedetti MS, Fornasini G, Wilding IR. The use of pharmacoscintigraphy to focus the development strategy for a novel 5-ASA colon targeting system (Time Clock system) J Control Release. 1997;49(2–3):115–122.
    1. Muraoka M, Hu Z, Shimokawa T, et al. Evaluation of intestinal pressure-controlled colon delivery capsule containing caffeine as a model drug in human volunteers. J Control Release. 1998;52(1–2):119–129. - PubMed
    1. You YC, Dong LY, Dong K, et al. In vitro and in vivo application of pH-sensitive colon-targeting polysaccharide hydrogel used for ulcerative colitis therapy. Carbohydr Polym. 2015;130:243–253. - PubMed

LinkOut - more resources