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Characterization of 5-fluorouracil microspheres for colonic delivery

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Abstract

The purpose of this investigation was to prepare and evaluate the colon-specific microspheres of 5-fluorouracil for the treatment of colon cancer. Core microspheres of alginate were prepared by the modified emulsification method in liquid paraffin and by cross-linking with calcium chloride. The core microspheres were coated with Eudragit S-100 by the solvent evaporation technique to prevent drug release in the stomach and small intestine. The microspheres were characterized by shape, size, surface morphology, size distribution, incorporation efficiency, and in vitro drug release studies. The outer surfaces of the core and coated microspheres, which were spherical in shape, were rough and smooth, respectively. The size of the core microspheres ranged from 22 to 55 μm, and the size of the coated microspheres ranged from 103 to 185 μm. The core microspheres sustained the drug release for 10 hours. The release studies of coated microspheres were performed in a pH progression medium mimicking the conditions of the gastrointestinal tract. Release was sustained for up to 20 hours in formulations with core microspheres to a Eudragit S-100 coat ratio of 1∶7, and there were no changes in the size, shape, drug content, differential scanning calorimetry thermogram, and in vitro drug release after storage at 40°C/75% relative humidity for 6 months.

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References

  1. Heidelberger C, Chaudhuri NK, Danneburg P, et al. Fluorinated pyrimidine. A new class of tumor inhibitory compounds. Nature. 1957; 179: 663–666.

    Article  CAS  Google Scholar 

  2. Langenbach RJ, Dancenberg PV, Heidelberger C. Thymidylate synthetase: mechanism of inhibition of 5-fluorouracil-2-deoxyuridylate. Biochem Biophys Res Commun. 1972; 48: 1565–1571.

    Article  CAS  Google Scholar 

  3. Parker WB, Cheng YC. Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther. 1990; 48: 381–395.

    Article  CAS  Google Scholar 

  4. Hahn RG, Moertel CG, Schutt AJ, Bruckner HW. A double-blind comparison of intensive course 5-fluorouracil by oral vs. intravenous route in the treatment of colorectal carcinoma. Cancer. 1975; 35: 1031–1035.

    Article  CAS  Google Scholar 

  5. Liu G, Fraussen E, Fitch MI, Warner E. Patient preferences for oral vs intravenous palliative chemotherapy. J Clin Oncol. 1997; 15: 110–115.

    CAS  Google Scholar 

  6. Van Cutsem E, Peeters M, Verslype C, Filez L, Haustermans K, Janssens J. The medical treatment of colorectal cancer: actual status and new developments. Hepatogastroenterology. 1999; 46: 709–716.

    Google Scholar 

  7. Labianca RF, Beretta GD, Pessi MA. Disease management consideration. Drugs. 2001; 61: 1751–1764.

    Article  CAS  Google Scholar 

  8. Diasio RB, Harris BE. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989; 16: 215–237.

    Article  CAS  Google Scholar 

  9. Yang L, Chu JS, Fix JA. Colon-specific drug delivery: new approaches and in vitro/in vivo evaluation. Int J Pharm. 2002; 235: 1–15.

    Article  CAS  Google Scholar 

  10. Shun YL, Ayres JW. Calcium alginate beads as core carriers of 5-aminosalicylic acid. Pharm Res. 1992; 9: 714–790.

    Google Scholar 

  11. Krishnaiah YSR, Satyanarayana V, Kumar DB, Karthikeyan RS, Bhaskar P. In vivo pharmacokinetics in human volunteers: oral administered guar gum-based colon-targeted 5-fluorouracil tablets. Eur J Pharm Sci. 2003; 19: 355–362.

    Article  CAS  Google Scholar 

  12. Madajewicz S, Petrelli N, Rustum YM, et al. Phase I–II trial of high dose calcium leucovorin and 5-fluorouracil in advanced colorectal cancer. Cancer Res. 1984; 44: 4667–4669.

    CAS  Google Scholar 

  13. Cortesi E, Aschelter AM, Gioacchini N, et al. Efficiency and toxicity of 5-fluorouracil and folates in advanced colon cancer. J Chemother. 1990; 2: 47–50.

    Google Scholar 

  14. O’Connell MJ, Mailliard JA, Kahn MJ, et al. Controlled trial of fluorouracil and low dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997; 15: 246–250.

    CAS  Google Scholar 

  15. Watts PJ, Barrow L, Steed KP, et al. The transit rate of different-sized model dosage forms through the human colon and effects of a lactulose induced catharsis. Int J Pharm. 1992; 87: 215–221.

    Article  CAS  Google Scholar 

  16. Calis S, Arica B, Kas HS, Hincal AA. 5-Fluorouracil-loaded alginate microspheres in chitosan gel for local therapy of breast cancer. In: Muzzarelli RAA, Muzzarelli C, eds. Chitosan in Pharmacy and Chemistry. Grottammare, Italy: Atec; 2002: 65–69.

    Google Scholar 

  17. Lorenzo-Lamosa ML, Remunan-Lopez C, Vila-Jato JL, Alonso MJ. Design of microencapsulated chitosan microspheres for colonic drug delivery. J Control Release. 1998; 52: 109–118.

    Article  CAS  Google Scholar 

  18. Martel P, Petit I, Pinguet S, Poujol S, Astre C, Fabbro M. Long term stability of 5-fluorouracil stored in PVC bags and in ambulatory pump reservoirs. J Pharm Biomed Anal. 1996; 14: 395–399.

    Article  CAS  Google Scholar 

  19. Matthews BR. Regulatory aspects of stability testing in Europe. Drug Dev Ind Pharm. 1999; 25: 831–856.

    Article  CAS  Google Scholar 

  20. Lin S, Kao Y. Solid particulates of drug-β-cyclodextrin inclusion complexes directly prepared by a spray-drying technique. Int J Pharm. 1989; 56: 249–259.

    Article  CAS  Google Scholar 

  21. Lemoine D, Wauters F, Bouchend S, Preat V. Preparation and characterization of alginate microspheres containing model antigen. Int J Pharm. 1998; 176: 9–19.

    Article  CAS  Google Scholar 

  22. Wagner JG. Interpretation of percent dissolved-time plots derived from in-vitro testing of conventional tablets and capsules. J Pharm Sci. 1969; 58: 1253–1257.

    Article  CAS  Google Scholar 

  23. Higuchi T. Mechanism of sustained action medication. J Pharm Sci. 1963; 52: 1145–1149.

    Article  CAS  Google Scholar 

  24. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983; 15: 25–35.

    Article  CAS  Google Scholar 

  25. Dubernet C. Thermo analysis of microspheres. Thermochim Acta. 1995; 248: 259–269.

    Article  Google Scholar 

  26. Mu L, Feng SS. Fabrication characterization and in vitro release of paclitaxel (Taxol) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers. J Control Release. 2001; 76: 239–254.

    Article  CAS  Google Scholar 

  27. Costa P, Labo JSMS. Modelling and comparison of dissolution profiles. Eur J Pharm Sci. 2001; 13: 123–133.

    Article  CAS  Google Scholar 

  28. Food and Drug Administration. Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms; 1997. Rockville, MD.

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Authors and Affiliations

  1. Department of Pharmaceutics, F/O Pharmacy, Hamdard University, 110063, New Delhi, India

    Ziyaur Rahman, Kanchan Kohli, Roop K. Khar, Mushir Ali, Naseem A. Charoo & Areeg A. A. Shamsher

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  1. Ziyaur Rahman
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  2. Kanchan Kohli
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  3. Roop K. Khar
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  4. Mushir Ali
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  5. Naseem A. Charoo
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  6. Areeg A. A. Shamsher
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Correspondence to Ziyaur Rahman.

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Published: May 26, 2006

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Rahman, Z., Kohli, K., Khar, R.K. et al. Characterization of 5-fluorouracil microspheres for colonic delivery. AAPS PharmSciTech 7, 47 (2006). https://doi.org/10.1208/pt070247

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  • DOI: https://doi.org/10.1208/pt070247

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