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AAPS PharmSciTech. 2007 June; 8(2): E143–E149.
Published online 2007 June 22. doi:  10.1208/pt0802048
PMCID: PMC2750363

Stomach-specific drug delivery of 5-fluorouracil using floating alginate beads


A multiple-unit-type oral floating dosage form (FDF) of 5-fluorouracil (5-FU) was developed to prolong gastric residence time, target stomach cancer, and increase drug bioavailability. The floating bead formulations were prepared by dispersing 5-FU together with calcium carbonate into a mixture of sodium alginate and hydroxypropyl methylcellulose solution and then dripping the dispersion into an acidified solution of calcium chloride. Calcium alginate beads were formed, as alginate undergoes ionotropic gelation by calcium ions and carbon dioxide develops from the reaction of carbonate salts with acid. The evolving gas permeated through the alginate matrix, leaving gas bubbles or pores, which provided the beads buoyancy. The prepared beads were evaluated for percent drug loading, drug entrapment efficiency, image, surface topography, buoyancy, and in vitro release. The formulations were optimized for different weight ratios of gas-forming agent and sodium alginate. The beads containing higher amounts of calcium carbonate demonstrated instantaneous, complete, and excellent floating ability over a period of 24 hours. The optimized formulation was subjected to in vivo antitumor studies to check the therapeutic efficacy of the floating dosage forms containing 5-FU against benzo(a)pyrene-induced stomach tumors in albino female mice (Balb/C strain). The multiple-bead FDF was found to reduce the tumor incidence in mice by 74%, while the conventional tablet dosage form reduced this incidence by only 25%. Results indicate that FDF performed significantly better than the simple tablet dosage form.

Keywords: 5-Fluorouracil, floating dosage form, calcium alginate beads, gastric residence time, buoyancy

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Selected References

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1. Soppimath KS, Kulkarni RA, Rudzinski WE, Aminabhavi TM. Microspheres as floating drug delivery systems to increase gastric retention of drugs. Drug Metab Rev. 2001;33:149–160. doi: 10.1081/DMR-100104401. [PubMed] [Cross Ref]
2. Deshpande AA, Rhodes CT, Shah NH, Malick AW. Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug Dev Ind Pharm. 1996;22:531–540. doi: 10.3109/03639049609108355. [Cross Ref]
3. Hwang SJ, Park H, Park K. Gastric retentive drug-delivery systems. Crit Rev Ther Drug Carrier Syst. 1998;15:243–284. [PubMed]
4. Sood A, Panchagnula R. Design of controlled release delivery systems using a modified pharmacokinetic approach: a case study for drugs having a short elimination half-life and a narrow therapeutic index. Int J Pharm. 2003;261:27–41. doi: 10.1016/S0378-5173(03)00267-9. [PubMed] [Cross Ref]
5. Choi BY, Park HJ, Hwang SJ, Park JB. Preparation of alginate beads for floating drug delivery system: effects of CO2 gas-forming agents. Int J Pharm. 2002;239:81–91. doi: 10.1016/S0378-5173(02)00054-6. [PubMed] [Cross Ref]
6. Ichikawa M, Watanabe S, Miyake Y. A new multiple-unit oral floating dosage form, I: preparation and evaluation of floating and sustained-release characteristics. J Pharm Sci. 1991;80:1062–1066. doi: 10.1002/jps.2600801113. [PubMed] [Cross Ref]
7. Badwan AA, Abumalooh A, Sallam E, Abukalaf A, Jawan O. A sustained release drug delivery system using calcium alginate beads. Drug Dev Ind Pharm. 1985;11:239–256. doi: 10.3109/03639048509056869. [Cross Ref]
8. Shiraishi S, Imai T, Otagiri M. Controlled release preparation of indomethacin using calcium alginate gel. Biol Pharm Bull. 1993;16:1164–1168. [PubMed]
9. Murata Y, Kofuji K, Kawashima S. Preparation of floating alginate beads for drug delivery to gastric mucosa. J Biomater Sci Polym Ed. 2003;14:581–588. doi: 10.1163/15685620360674263. [PubMed] [Cross Ref]
10. Murata Y, Sasaki N, Miyamoto E, Kawashima S. Use of floating alginate beads for stomach-specific drug delivery. Eur J Pharm Biopharm. 2000;50:221–226. doi: 10.1016/S0939-6411(00)00110-7. [PubMed] [Cross Ref]
11. Stops F, Fell JT, Collett JH, Martini LG, Sharma HL, Smith AM. Citric acid prolongs the gastro-retention of a floating dosage form and increases bioavailability of riboflavin in the fasted state. Int J Pharm. 2006;308:14–24. doi: 10.1016/j.ijpharm.2005.09.039. [PubMed] [Cross Ref]
12. Tønnesen HH, Karlsen J. Alginate in drug delivery systems. Drug Dev Ind Pharm. 2002;28:621–630. doi: 10.1081/DDC-120003853. [PubMed] [Cross Ref]
13. Giunchedi P, Gavini E, Moretti MDL, Pirisino G. Evaluation of alginate compressed matrices as prolonged drug delivery systems.AAPS PharmSciTech. 2000;1:article 19. [PMC free article] [PubMed]
14. Halder A, Mukherjee S, Sa B. Development and evaluation of polyethyleneimine-treated calcium alginate beads for sustained release of diltiazem. J Microencapsul. 2005;22:67–80. doi: 10.1080/02652040500045003. [PubMed] [Cross Ref]
15. Streubel A, Siepmann J, Bodmeier R. Multiple unit gastroretentive drug delivery systems: a new preparation method for low density microparticles. J Microencapsul. 2003;20:329–347. doi: 10.1080/0265204021000058384. [PubMed] [Cross Ref]
16. Dollery C, editor. Therapeutic Drugs. 2nd ed. Edinburg, UK: Churchill Livingstone, Harcourt Brace and Company; 1999. pp. F103–F108.
17. Parfitt K, editor. Martindale, The Complete Drug Reference. 32nd ed. London, UK: Pharmaceutical Press; 1999. pp. 534–537.
18. Krishnaiah YSR, Satyanarayan V, Kumar BD, Karthikeyan RS. In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil. Eur J Pharm Sci. 2002;16:185–192. doi: 10.1016/S0928-0987(02)00081-7. [PubMed] [Cross Ref]
19. Triano A, Simpson JB, Krathy M, Lang WR, Triolo AJ. Protective effects of trifluralin on benzo(a)pyrene-induced tumors in A/J mice. Cancer Res. 1985;45:601–607. [PubMed]
20. Wattenberg LW. Inhibition of carcinogenic and toxic effects of polycyclic hydrocarbons by phenolic antioxidants and ethoxyquin. J Natl Cancer Inst. 1972;48:1425–1430. [PubMed]
21. Deshpande SS, Ingle AD, Maru GB. Inhibitory effects of curcumin-free aqueous turmeric extract on benzo(a)pyrene-induced forestomach papillomas in mice. Cancer Lett. 1997;118:79–85. doi: 10.1016/S0304-3835(97)00238-3. [PubMed] [Cross Ref]
22. Halder A, Maiti S, Sa B. Entrapment efficiency and release characteristics of polyethyleneimine-treated or untreated calcium alginate beads loaded with propranolol-resin complex. Int J Pharm. 2005;302:84–94. doi: 10.1016/j.ijpharm.2005.06.020. [PubMed] [Cross Ref]
23. Singh B, Singh S. A comprehensive computer program for the study of drug release kinetics from compressed matrices. Ind J Pharm Sci. 1998;60:358–362.
24. Peppas NA, Sahlin JJ. A simple equation for the description of solute release, III: coupling of diffusion and relaxation. Int J Pharm. 1989;57:169–172. doi: 10.1016/0378-5173(89)90306-2. [Cross Ref]
25. Blanco MD, Sastre RL, Teijon C, Olmo R, Teijon JM. 5-Fluorouracil-loaded microspheres prepared by spray-drying poly (D,L-lactide) and poly (lactide-co-glycolide) polymers: characterization and drug release. J Microencapsul. 2005;22:671–682. doi: 10.1080/02652040500161990. [PubMed] [Cross Ref]
26. Poncelet D, Babak V, Dulieu C, Picot A. A physicochemical approach to production of alginate beads by emulsification-internal ionotropic gelation. Colloids Surf A. 1999;155:171–176. doi: 10.1016/S0927-7757(98)00709-2. [Cross Ref]

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