Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2007 September; 8(3): E34–E41.
Published online 2007 July 13. doi:  10.1208/pt0803056
PMCID: PMC2750552

Design and development of hydrogel beads for targeted drug delivery to the colon


The purpose of this research was to develop and evaluate a multiparticulate system of chitosan hydrogel beads exploiting pH-sensitive property and specific biodegradability for colon-targeted delivery of satranidazole. Chitosan hydrogel beads were prepared by the cross-linking method followed by enteric coating with Eudragit S100. All formulations were evaluated for particle size, encapsulation efficiency, swellability, and in vitro drug release. The size of the beads was found to range from 1.04±0.82 mm to 1.95±0.05 mm. The amount of the drug released after 24 hours from the formulation was found to be 97.67%±1.25% in the presence of extracellular enzymes as compared with 64.71%±1.91% and 96.52%±1.81% release of drug after 3 and 6 days of enzyme induction, respectively, in the presence of 4% cecal content. Degradation of the chitosan hydrogel beads in the presence of extracellular enzymes as compared with rat cecal and colonic enzymes indicates the potential of this multiparticulate system to serve as a carrier to deliver macromolecules specifically to the colon and can be offered as a substitute in vitro system for performing degradation studies. Studies demonstrated that orally administered chitosan hydrogel beads can be used effectively for the delivery of drug to the colon.

Keywords: Chitosan, pH-sensitive polymer, colon-specific drug delivery, hydrogel beads, multiparticulate system, satranidazole

Full Text

The Full Text of this article is available as a PDF (373K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Davis SS. Assessment of gastrointestinal transit and drug absorption. In: Prescott LF, Nimmo WS, editors. Novel Drug Delivery and Its Therapeutic Application. Chichester, UK: Wiley; 1990. pp. 89–101.
2. Chourasia MK, Jain SK. Pharmaceutical approaches to colon targeted drug delivery systems. J Pharm Pharm Sci. 2003;6:33–66. [PubMed]
3. Davaran S, Hanaee J, Khosravi A. Release of 5-amino salicylic acid from acrylic type polymeric prodrugs designed for colon-specific drug delivery. J Control Release. 1999;58:279–287. doi: 10.1016/S0168-3659(98)00167-9. [PubMed] [Cross Ref]
4. Schacht E, Gevaert A, Kenawy ER, et al. Polymers for colon specific drug delivery. J Control Release. 2007;39:327–338. doi: 10.1016/0168-3659(95)00184-0. [Cross Ref]
5. Chung KT, Stevens SE, Cerniglia CE. The reduction of azo dyes by the intestinal microflora. Crit Rev Microbiol. 1992;18:175–190. doi: 10.3109/10408419209114557. [PubMed] [Cross Ref]
6. Yamaoka T, Makita Y, Sasatani H, Kim SI, Kimura Y. Linear type azo-containing polyurethane as drug-coating material for colon-specific delivery: its properties degradation behavior and utilization for drug formulation. J Control Release. 2000;66:187–197. doi: 10.1016/S0168-3659(99)00270-9. [PubMed] [Cross Ref]
7. Shantha KL, Ravichandran P, Rao KP. Azo polymeric hydrogels for colon targeted drug delivery. Biomaterials. 1995;16:1313–1318. doi: 10.1016/0142-9612(95)91046-2. [PubMed] [Cross Ref]
8. Van den Mooter G, Samyn C, Kinget R. Azo, polymers for colon-specific drug delivery. Int J Pharm. 1992;87:37–46. doi: 10.1016/0378-5173(92)90225-Q. [Cross Ref]
9. Jain A, Gupta Y, Jain SK. Azo-chemistry and its potential for colonic delivery. Crit Rev Ther Drug Carrier Syst. 2006;23:349–400. [PubMed]
10. Ghandehari H, Kopeckova P, Kopecek J. In vitro-degradation of pH sensitive hydrogels containing aromatic azo bonds. Biomaterials. 1997;18:861–872. doi: 10.1016/S0142-9612(97)00007-0. [PubMed] [Cross Ref]
11. Kakoulides EP, Smart JD, Tsibouklis J. Azocrosslinked poly(acrylic acid) for colonic delivery and adhesion specificity synthesis and characterization. J Control Release. 1998;52:291–300. doi: 10.1016/S0168-3659(98)00005-4. [PubMed] [Cross Ref]
12. Chaurasia M, Chourasia MK, Jain NK, et al. Cross-linked guar gum microspheres: a viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer. AAPS PharmSciTech. 2006;7:74–74. doi: 10.1208/pt070374. [PMC free article] [PubMed] [Cross Ref]
13. Shimono N, Takatori T, Masumi T, et al. Chitosan dispersed system for colon-specific drug delivery. Int J Pharm. 2002;245:45–54. doi: 10.1016/S0378-5173(02)00344-7. [PubMed] [Cross Ref]
14. Tozaki H, Komoike J, Tada C, et al. Chitosan capsules for colon-specific drug delivery: Improvement of insulin absorption from the rat colon. J Pharm Sci. 1997;86:1016–1021. doi: 10.1021/js970018g. [PubMed] [Cross Ref]
15. Jain A, Gupta Y, Jain SK. Potential of calcium pectinate beads for target specific drug release to colon. J Drug Target. 2007;15:285–294. doi: 10.1080/10611860601146134. [PubMed] [Cross Ref]
16. Rubinstein A. Microbially controlled drug delivery to the colon. Biopharm Drug Dispos. 1990;11:465–475. doi: 10.1002/bdd.2510110602. [PubMed] [Cross Ref]
17. Ashford M, Fell JT, Attwood D, Sharma H, Woodhead P. Anin vivo investigation into the suitability of pH-dependent polymers for colonic targeting. Int J Pharm. 1993;95:193–199. doi: 10.1016/0378-5173(93)90406-6. [Cross Ref]
18. Furda I. Aminopolysaccharides—their potential as dietary fiber. In: Furda I, editor. Unconventional Sources of Dietary Fiber, Physiological and In vitro Functional Properties. Washington, DC: American Chemical Society; 1983. pp. 105–122.
19. Ormrod DJ, Holmes CC, Miller TE. Dietary chitosan inhibits hypercholesterolaemia and atherogenesis in the apolipoprotein E-deficient mouse model of atherosclerosis. Atherosclerosis. 1998;138:329–334. doi: 10.1016/S0021-9150(98)00045-8. [PubMed] [Cross Ref]
20. Yamamoto A, Tozaki H, Okada N, Fujita T. Colon specific delivery of peptide drugs and anti-inflammatory drugs using chitosan capsules. STP Pharma Sciences. 2000;10:23–43.
21. Tozaki H, Odoriba T, Okada N, et al. Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats. J Control Release. 2002;82:51–61. doi: 10.1016/S0168-3659(02)00084-6. [PubMed] [Cross Ref]
22. Fernandez-Hervas MJ, Fell JT. Pectin/chitosan mixtures as coatings for colon-specific drug delivery: anin vitro evaluation. Int J Pharm. 1998;169:115–119. doi: 10.1016/S0378-5173(98)00114-8. [Cross Ref]
23. Davis SS, Hardy JG, Fara JW. Transit of pharmaceutical dosage forms through the small intestine. Gut. 1986;27:886–892. doi: 10.1136/gut.27.8.886. [PMC free article] [PubMed] [Cross Ref]
24. Zhang H, Ibrahim A, Alsarra S, Neau H. An in vitro evaluation of a chitosan-containing multiparticulate system for macromolecule delivery to the colon. Int J Pharm. 2002;239:197–205. doi: 10.1016/S0378-5173(02)00112-6. [PubMed] [Cross Ref]
25. Huyghebaert N, Vermeire A, Remon JP. In vitro evaluation of coating polymers for enteric coating and human ileal targeting. Int J Pharm. 2005;298:26–37. doi: 10.1016/j.ijpharm.2005.03.032. [PubMed] [Cross Ref]
26. Prizont R, Konigsberg N. Identification of bacterial glycosidases in rat caecal contents. Dig Dis Sci. 1981;26:773–777. doi: 10.1007/BF01309607. [PubMed] [Cross Ref]
27. Mason VC. Some observations on the distribution and origin of nitrogen in sheep feces. J Agric Sci. 1969;73:99–111. doi: 10.1017/S0021859600024175. [Cross Ref]
28. Salyers AA, Palmer JK, Wilkins TD. Degradation of polysaccharides by intestinal bacterial enzymes. Am J Clin Nutr. 1978;31:S128–S130. [PubMed]
29. Chourasia MK, Jain SK. Design and development of multiparticulate system for targeted drug delivery to colon. Drug Deliv. 2004;11:201–207. doi: 10.1080/10717540490445955. [PubMed] [Cross Ref]
30. Sezer AD, Akbuga J. Release characteristics of chitosan treated alginate beads: I. Sustained release of a macromolecular drug from chitosan treated alginate beads. J Microencapsul. 1999;16:195–203. doi: 10.1080/026520499289176. [PubMed] [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists