Skip to main content

Advertisement

SpringerLink
Log in

Bioadhesive Dosage Forms for Esophageal Drug Delivery

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

No Heading

The esophagus as a site for drug delivery has been much overlooked in comparison to the remainder of the gastrointestinal tract. The low permeability and transient nature of the esophagus means that it is unsuitable for delivery of drugs for systemic action. However, esophageal disorders including fungal infection, cancers, motility dysfunction, and damage due to gastric reflux may be treated using locally acting agents that offer benefits of reduced dosage and decreased side effects. Bioadhesive dosage forms that adhere to the esophageal mucosa and prolong contact have been investigated to improve the efficacy of locally acting agents. The rationale for local esophageal drug delivery and its limitations, the factors that determine adhesion to this organ, and the experimental models used in esophageal drug delivery research are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. 1. Q. Li, J. A. Castell, and D. O. Castell. Manometric determination of esophageal length. Am. J. Gastroenterol. 89:722–725 (1994).

    Google Scholar 

  2. 2. N. Washington, C. Washington, and C. G. Wilson. Oesophageal transit. In N. Washington, C. Washington, and C. G. Wilson (eds.), Physiological Pharmaceutics; Barriers to Drug Absorption, Taylor & Francis, London, 2001, pp. 59–73.

    Google Scholar 

  3. 3. S. Kuna. The pH of gastric juice in the normal resting state. Arch. Int. Pharmacodyn. 151:79–97 (1964).

    Google Scholar 

  4. 4. P. J. Kahrilas. Functional anatomy and physiology of the esophagus. In: D.O. Castell (ed.), The Esophagus, 2nd ed., Little, Brown, Boston, 1995, pp. 1–28.

    Google Scholar 

  5. 5. J. L. O’Neill and T. L. Remington. Drug-induced esophageal injuries and dysphagia. Ann. Pharmacother. 37:1675–1683 (2003).

    Google Scholar 

  6. 6. T. A. Woltman, B. K. Oelschlager, and C. A. Pellegrini. Surgical management of esophageal motility disorders. J. Surg. Res. 117:34–43 (2004).

    Google Scholar 

  7. 7. J. W. Kikendall, A. C. Friedman, M. A. Oyewole, D. Fleischer, and L. F. Johnson. Pill-induced oesophageal injury: case reports and review of the medical literature. Dig. Dis. Sci. 28:174–182 (1983).

    Google Scholar 

  8. 8. S. Nandurkar and N. J. Talley. Epidemiology and natural history of reflux disease. Best Pract. Res. Cl. Ga. 15(5):743–757 (2000).

    Google Scholar 

  9. 9. A. Van der Burgh, J. Dees, W. C. J. Hop, and M. van Blankenstein. Oesophageal cancer is an uncommon cause of death in patients with Barrett’s esophagus. Gut 39:5–8 (1996).

    Google Scholar 

  10. 10. M. Conio, G. Lapertosa, S. Blanchi, and R. Filiberti. Barrett’s esophagus: an update. Crit. Rev. Oncol. Hematol. 46:187–206 (2003).

    Google Scholar 

  11. 11. I. T. Johnson. New approaches to the role of diet in the prevention of cancers of the alimentary tract. Mutat. Res. 551:9–28 (2004).

    Google Scholar 

  12. 12. J. P. Moorman. Diagnosis and pharmacotherapy of infectious esophagitis. In G. Friedman, E. D. Jacobson, and R. W. McCallum (eds.), Gastrointestinal Pharmacology and Therapeutics, Lippincott-Raven, New York, 1997 pp. 201–213.

    Google Scholar 

  13. 13. Wellmark Report 2003. Available at http://www.wellmark.com/health_improvement/reports/ppi/about.htm#prior (accessed 14/10/2004).

  14. 14. C. O. H. Russell, L. D. Hill, E. R. Holmes, D. A. Hull, R. Gannon, and C. E. Pope. Radionuclide transit: a sensitive screening test for esophageal dysfunction. Gastroenterology 80:887–892 (1981).

    Google Scholar 

  15. 15. K. T. Evans and G. M. Roberts. The ability of patients to swallow capsules. J. Clin. Hosp. Pharm. 6:207–208 (1981).

    Google Scholar 

  16. 16. G. S. McCord and R. E. Clouse. Pill-induced esophageal strictures: clinical features and risk factors for development. Am. J. Med. 88:512–518 (1990).

    Google Scholar 

  17. 17. M. Marvola, K. Vahervuo, A. Sothmann, E. Martilla, and M. Rajaniemi. Development of a method for study of the tendency of drug products to adhere to the esophagus. J. Pharm. Sci. 71:975–977 (1982).

    Google Scholar 

  18. 18. H. Al-Dujaili, A. T. Florence, and E. G. Salole. The adhesiveness of proprietary tablets and capsules to porcine oesophageal tissue. Int. J. Pharm. 34:75–79 (1986).

    Google Scholar 

  19. 19. M. Weinbeck, W. Berges, and H. J. Lubke. Drug-induced oesophageal lesions. Balliere Clin. Gastr. 2:263–274 (1988).

    Google Scholar 

  20. 20. O. Honkanen, P. Laaksonen, J. Marvola, S. Eerikainene, R Tuominen, and M. Marvola. Bioavailability and in vitro oesophageal sticking tendancy of hydroxypropyl methylcellulose capsule formulations and corresponding gelatine capsule formulations. Eur. J. Pharm. Sci. 15:479–488 (2002).

    Google Scholar 

  21. 21. L. McCargar, D. Crail, R. Dansereau, W. Myers, and M. Lane. The in-vitro porcine adhesion model is not predictive of the esophageal transit of risedronate tablets in humans. Int. J. Pharm. 222:191–197 (2001).

    Google Scholar 

  22. 22. D. A. Swisher, S. L. Sendelbeck, and J. W. Fara. Adherence of various oral dosage forms to the esophagus. Int. J. Pharm. 22:219–228 (1984).

    Google Scholar 

  23. 23. M. Marvola, M. Rajaniemi, E. Martilla, K. Vahervuo, and A. Sothmann. Effect of dosage form and formulation factors on the adherence of drugs to the esophagus. J. Pharm. Sci. 72:1034–1036 (1983).

    Google Scholar 

  24. 24. S. Mathias, S. A. Young, J. Tsibouklis, and J. D. Smart. Adhesion of formulation coatings to the oesophagus: a novel in vitro test system. J. Pharm. Pharmacol. 54:34 (2002).

    Google Scholar 

  25. 25. A. C. Perkins, C. G. Wilson, M. Frier, P. E. Blackshaw, R. J. Dansereau, R. M. Vincent, D. Wenderoth, S. Hathaway, Z. Li, and R. C. Spiller. The use of scintigraphy to demonstrate the rapid esophageal transit of the oval film-coated placebo risedronate tablet compared to a round uncoated placebo tablet when administered with minimal volumes of water. Int. J. Pharm. 222:295–303 (2001).

    Google Scholar 

  26. 26. O. Honkanen, J. Marvola, H. Kanerva, K. Lindevall, M. Lipponene, T. Kekki, A. Ahonen, and M. Marvola. Gamma scintigraphic evaluation of the fate of hydroxypropyl methyl cellulose capsules in the human gastrointestinal tract. Eur. J. Pharm. Sci. 21:671–678 (2004).

    Google Scholar 

  27. 27. M. Sakkinen, J. Marvola, H. Kanerva, K. Lindevall, M. Lipponene, A. Ahonen, and M. Marvola. Scintigraphic verification of adherence of a chitosan formulation to the human oesophagus. Eur. J. Pharm. Biopharm. 57:145–147 (2004).

    Google Scholar 

  28. 28. K. S. Channer and J. P. Virdee. The effect of formulation on oesophageal transit. J. Pharm. Pharmacol. 37:126–129 (1985).

    Google Scholar 

  29. 29. R. Ito, Y. Machida, T. Sannan, and T. Nagai. Magnetic granules: a novel system for specific drug delivery to esophageal mucosa in oral administration. Int. J. Pharm. 61:109–117 (1990).

    Google Scholar 

  30. 30. V. Vonarx, S. Eleouet, J. Carre, P. Ioss, A. Gouyette, A. M. Leray, C. Merle, Y. Lajat, and T. Patrice. Potential efficacy of a delta 5-aminolevulinic acid bioadhesive gel formulation for the photodynamic treatment of lesions of the gastrointestinal tract in mice. J. Pharm. Pharmacol. 49:652–656 (1997).

    Google Scholar 

  31. 31. A. M. Potts, S. Jackson, N. Washington, P. Gilchrist, E. S. Ron, M. Schiller, and C. Wilson. The oesophageal retention of a thermally sensitive hydrogel. J. Pharm. Pharmacol. 49:77 (1997).

    Google Scholar 

  32. 32. D. J. Dobrozsi, R. L. Smith, and A. A. Sakr. Comparative mucoretention of sucralfate suspensions in an everted rat esophagus model. Int. J. Pharm. 189:81–89 (1999).

    Google Scholar 

  33. 33. H. K. Batchelor, D. Banning, P. W. Dettmar, F. C. Hampson, I. G. Jolliffe, and D. Q. M. Craig. An in vitro mucosal model for prediction of the bioadhesion of alginate solutions to the oesophagus. Int. J. Pharm. 238:123–132 (2002).

    Google Scholar 

  34. 34. D. Banning, D. Q. M. Craig, P. W. Dettmar, F. C. Hampson, and E. Onsoyen. An in vitro evaluation of the bioadhesive properties of sodium alginate solution on porcine esophagus. Annual Meeting Abstracts, American Association of Pharmaceutical Scientists. Pharm. Sci. Suppl. 1:S426 (1997).

    Google Scholar 

  35. 35. S. A. Young and J. D. Smart. The porcine oesophageal mucoadhesive test system: a novel in vitro apparatus for the evaluation of liquid and semisolid formulations. J. Pharm. Pharmacol. 20:167 (1998).

    Google Scholar 

  36. 36. J. D. Smart, R. G. Riley, J. Tsibouklis, S. A. Young, F. C. Hampson, J. A. Davies, G. Kelly, P. W. Dettmar, and W. R. Wilber. The retention of 14 C-labelled poly(acrylic acids) on gastric and oesophageal mucosa: an in vitro study. Eur. J. Pharm. Sci. 20:83–90 (2004).

    Google Scholar 

  37. 37. A. M. Potts, B. O’Mahony, J. Foster, C. G. Wilson, and H. N. E. Stevens. The use of magnetic resonance imaging (MRI) to visualise the oesophageal transit of liquid and gel formulations. J. Pharm. Pharmacol. 52:18 (2000).

    Google Scholar 

  38. 38. S. A. Mortazavi and J. D. Smart. An investigation of some factors influencing the in vitro assessment of mucoadhesion. Int. J. Pharm. 116:223–230 (1995).

    Google Scholar 

  39. 39. J. C. Richardson, P. W. Dettmar, F. C. Hampson, and C. D. Melia. Oesophageal bioadhesion of sodium alginate suspensions: 2. Suspension behaviour on oesophageal mucosa. Eur. J. Pharm. Sci. 23:49–56 (2004).

    Google Scholar 

  40. 40. I. D. Hill, P. P. Walters, and D. G. Brown. Ultramulsion based ingestible compositions. U.S. Patent No. 5711936 (1998).

  41. 41. R. C. Cuca, K. S. Lienhop, T. C. Riley, M. I. Kirschner, and R. S. Levinson. Long acting GI and esophageal protectant. U.S. Patent No. 5858391 (1999).

  42. 42. T. H. Stanley and B. Hague. Non-dissolvable drug-containing dosage-forms for use in the transmucosal delivery of a drug to a patient. U.S. Patent No. 5855908 (1999).

  43. 43. S. E. Ron, L. Bromberg, and M. Temchenko. End modified thermal responsive hydrogels. U.S. Patent No. 6316011 (2001).

  44. 44. D. J. Dobrozsi. Oral liquid mucoadhesive compounds. U.S. Patent No. 6319513 (2001).

  45. 45. P. W. Dettmar, P. A. Dickinson, F. C. Hampson, and I. G. Jolliffe. Compositions for treatment of disorders of the oesophagus. U.S. Patent No. 6610667 (2003).

  46. 46. S. I. Pather, J. R. Robinson, J. D. Eichman, R. K. Khankari, J. Honz, and S. V. Gupte. Effervescent drug delivery system for oral administration. U.S. Patent No. 6641838 (2003).

  47. 47. P. Iooss, A Gouyette, A. M. LeRay, T. Patrice, and C. Merle. Bioadhesive polymers as platforms for oral Barrett’s oesophagus treatment, formulation and evaluation of various water-soluble bioadhesive polymers. Proceedings 1st World Meeting APGI/APV. APV Press, Budapest, 1995, pp. 829–830.

    Google Scholar 

  48. 48. H. Nagano, Y. Machida, M. Iwata, T. Imada, Y. Noguchi, A. Matsumoto, and T. Nagai. Preparation of magnetic granules containing bleomycin and its evaluation using model esophageal cancer. Int. J. Pharm. 147:119–125 (1997).

    Google Scholar 

  49. 49. H. K. Batchelor, M. Tang, P. W. Dettmar, F. C. Hampson, I. G. Jolliffe, and D. Q. M. Craig. Feasibility of a bioadhesive drug delivery system targeted to oesophageal tissue. Eur. J. Pharm. Biopharm. 57:295–298 (2004).

    Google Scholar 

  50. 50. B. Vandergam, D. Gibbs, M. Valtonene, H. Jager, and O. Armignacco. Fluconazole orally dispersible tablets for the treatment of patients with oropharyngeal candidiasis. J. Int. Med. Res. 26:209–218 (1998).

    Google Scholar 

  51. 51. L. Zhang and H. K. Batchelor. A bioadhesive formulation for the delivery of anti-fungal agents to the oesophagus. J. Pharm. Pharmacol. 56:44 (2004).

    Google Scholar 

  52. 52. J. W. Kikendall and M. H. Mellow. Effect of sublingual nitroglycerin and long-acting nitrate preparations on esophageal motility. Gasteroenterology 79:703–706 (1980).

    Google Scholar 

  53. 53. A. M. Potts, G. G. Wilson, H. N. E. Stevens, D. J. Dobrozsi, N. Washington, M. Frier, and A. C. Perkins. Oesophageal bandaging: a new opportunity for thermosetting polymers. STP Pharm. Sci. 10:293–301 (2000).

    Google Scholar 

  54. 54. M. Tang, P. W. Dettmar, and H. K. Batchelor. A bioadhesive alginate layer on the oesophagus can reduce damage caused by acid reflux. Proceedings of Pharmaceutical Sciences World Congress, Kyoto, PSWC, Japan, 2004, p. 214.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medicines Research Unit, Aston University, Birmingham, B4 7ET, UK

    Hannah Batchelor

Authors
  1. Hannah Batchelor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hannah Batchelor.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Batchelor, H. Bioadhesive Dosage Forms for Esophageal Drug Delivery. Pharm Res 22, 175–181 (2005). https://doi.org/10.1007/s11095-004-1183-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-004-1183-5

Key Words:

Search

Navigation