Pharmaceutical Research

, Volume 8, Issue 1, pp 101–105 | Cite as

Jejunal Absorption, Pharmacological Activity, and Pharmacokinetic Evaluation of Indomethacin-Loaded Poly(d,l-Lactide) and Poly(Isobutyl-Cyanoacrylate) Nanocapsules in Rats

  • Nazih Ammoury
  • Hatem Fessi
  • Jean-Philippe Devissaguet
  • Marcelle Dubrasquet
  • Simon Benita
Article

Abstract

The jejunal absorption of indomethacin nanocapsules was studied using an in vivo infusion technique. Jejunal absorption of indomethacin from the nanocapsules was slightly delayed as compared to a commercial indomethacin solution. The plasma and jejunal mucosa indomethacin concentrations were similar in both cases. However, the nanocapsules protected the rat jejunum from the ulcerating effect of indomethacin, probably by avoiding direct contact of the free drug with the surface of the mucosa. The pharmacokinetic profile of indomethacin nanocapsule formulations was compared to a solution of free drug following oral administration of 5 mg/kg in rats; no difference in the mean concentration–time profiles of the drug was observed. Blood levels of thromboxane showed a sustained biological activity, over a period of 24 hr, of indomethacin-loaded nanocapsules, relative to the drug in solution, following oral administration.

indomethacin polymeric nanocapsules jejunal absorption oral pharmacokinetics thromboxane intestinal lesions 

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REFERENCES

  1. 1.
    N. Al-Khouri Fallouh, L. Roblot-Treupel, H. Fessi, J.-P. Devissaguet, and F. Puisieux. Development of a new process for the manufacture of polyisobutylcyanoacrylate nanocapsules. Int. J. Pharm. 28:125–132 (1986).Google Scholar
  2. 2.
    J. F. Woodley. Liposomes for oral administration of drugs. CRC Crit. Rev. Ther. Drug Carrier Syst. 2:1–18 (1986).Google Scholar
  3. 3.
    M. Aprahamian, C. Michel, W. Humbert, J.-P. Devissaguet, and C. Damgé. Transmucosal passage of polyalkylcyanoacrylate nanocapsules as a new drug carrier in the small intestine. Biol. Cell 61:69–76 (1987).Google Scholar
  4. 4.
    H. Fessi, F. Puisieux, J.-P. Devissaguet, N. Ammoury, and S. Benita. Nanocapsule formation by interfacial deposition following solvent displacement. Int. J. Pharm. 55:R1–R4 (1989).Google Scholar
  5. 5.
    M.-M. Gallardo, L. Roblot-Treupel, J. Mahuteau, I. Genin, P. Couvreur, M. Plat, and F. Puisieux. Nanocapsules et nanosphères d'alkylcyanoacrylate, interactions principe actif/polymère. Proc., APGI, 5th Int. Conf. Pharm. Technol., Paris, 1989, Vol. IV, pp. 36–45.Google Scholar
  6. 6.
    E. C. Soehngen, E. Godin-Ostro, F. G. Fielder, R. S. Ginsberg, M. A. Slusher, and A. L. Weiner. Encapsulation of indomethacin in liposomes provides protection against both gastric and intestinal ulcerations when orally administered to rats. Arth. Rheum. 31:414–421 (1988).Google Scholar
  7. 7.
    M. E. Goldyne. Prostaglandins and other eicosanoids. In B. G. Katzung (ed.), Basic and Clinical Pharmacology, 2nd ed. Lange Medical, Los Altos, CA, 1984, pp. 217–226.Google Scholar
  8. 8.
    A. Drouet, M. LeDuff, R. LeVerge, and J.-P. Devissaguet. Application de la H.P.L.C. à l'étude de la clométacine chez l'homme. In J. M. Aiache and J. Hirtz (eds.), Proc. First Eur. Cong. Biopharm. Pharmacokin., Clermont-Ferrand, France, 1981, Vol. 2, pp. 502–507.Google Scholar
  9. 9.
    N. Ammoury, H. Fessi, J.-P. Devissaguet, F. Puisieux, and S. Benita. Physicochemical characterization of polymeric nanocapsules and in vitro release evaluation of indomethacin as a drug model. STP Pharm. 5 (10):647–651 (1989).Google Scholar
  10. 10.
    S. Benita, A. Rubinstein, Y. V. Palhek, and A. Reches. The influence of perfusion location and perfusate on the absorption of physostigmine from submicronized emulsion and solution in the rat intestine. Proc., APGI, 4th Int. Conf. Pharm. Technol., Paris, 1989, Vol. III, pp. 76–83.Google Scholar
  11. 11.
    P. Del Soldato, A. Meli, and G. Volterra. Influence of fasting and cimetidine on the relationship between ulcerogenic and anti-inflammatory properties of indomethacin. Br. J. Pharm. 67:33–37 (1979).Google Scholar
  12. 12.
    P. Pradelles, J. Grassi, and J. Maclouf. Enzyme immunoassays of eicosanoids using acetylcholinesterase as label: An alternative to radioimmunoassay. Anal. Chem. 57:1170–1173 (1985).Google Scholar
  13. 13.
    N. Ammoury, H. Fessi, J.-P. Devissaguet, F. Puisieux, and S. Benita. In vitro release pattern of indomethacin from poly (D,L-lactide) nanocapsules. J. Pharm. Sci. 79:763–767 (1990).Google Scholar
  14. 14.
    H. B. Hucker, A. G. Zacchei, S. V. Cox, D. A. Brodie, and N. H. R. Cantwell. Studies on the absorption, distribution and excretion of indomethacin in various species. J. Pharmacol. Exp. Ther. 153 (2):237–249 (1966).Google Scholar
  15. 15.
    V. Andrieu, M. Dubrasquet, H. Fessi, and J.-P. Devissaguet. Etude pharmacocinétique, biopharmaceutique et de tolérance digestive de dispersions colloïdales d'indométacine. Proc., APGI, 4th Int. Conf. Pharm. Technol., Paris, 1986, Vol. IV, pp. 166–174.Google Scholar
  16. 16.
    V. Andrieu, H. Fessi, M. Dubrasquet, J.-P. Devissaguet, F. Puisieux, and S. Benita. Pharmacokinetic evaluation of indomethacin nanocapsules. Drug Design Deliv. 4:295–302 (1989).Google Scholar

Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Nazih Ammoury
    • 1
  • Hatem Fessi
    • 1
  • Jean-Philippe Devissaguet
    • 1
  • Marcelle Dubrasquet
    • 2
  • Simon Benita
    • 3
  1. 1.Laboratoire de Pharmacie Galénique et BiopharmacieURA CNRS 1218, Centre d’Etudes PharmaceutiquesChatenay-Malabry CedexFrance
  2. 2.Unité de Gastro-EntérologieParisFrance
  3. 3.Pharmacy Department, School of PharmacyThe Hebrew University of JerusalemJerusalemIsrael

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