Abstract
The intestinal absorption of cyclosporine was measured in situ in rats using an olive oil emulsion prepared by either stirring or homogenization. The surface area of the homogenized dosage form was twice that of the stirred dosage form. The apparent permeability of cyclosporine from the homogenized emulsion was about twice that of the emulsion prepared by stirring. The examination of absorption in different intestinal segment lengths suggested the presence of an “absorption window.” The absorption of cyclosporine appeared to be concentration independent and, therefore, non-carrier mediated. The dependence of absorption upon the intestinal perfusion rate suggested that the stagnant aqueous layer is the rate-limiting barrier in cyclosporine absorption. These results indicate that the bioavailability of cyclosporine administered in an emulsion can possibly be increased by enhancing its rate of absorption through the reduction of droplet size.
Similar content being viewed by others
REFERENCES
R. J. Ptachcinski, R. Venkataramanan, and G. J. Burckart. Clin. Pharmacokinetics 11:107–132 (1986).
J. Newberger and B. D. Kahan. Trans. Proc. 15:2413–2415 (1983).
C. T. Ueda, M. Lemaire, G. Gsell, P. Misslin, and K. Nussbaumer. Biopharm. Drug Disp. 5:141–151 (1984).
P. J. Carrigan and T. R. Bates. J. Pharm Sci. 62:1476–1479 (1973).
A. C. Frazer, J. H. Schulman, and A. C. Stewart. J. Physiol. (London) 103:306–310 (1944).
J. H. Deuel (ed.). The Lipids: Their Chemistry and Biochemistry, Vol. 2, Interscience, New York, 1955, p. 282.
B. Borgstrom. J. Clin. Invest. 39:309–313 (1960).
I. McColl and G. E. Sladen (eds.). Intestinal Absorption in Man, Academic Press, New York, 1975, pp. 187–221.
R. J. Sawchuk and W. M. Awni. J. Pharm. Sci. 75:1151–1155 (1986).
N. F. H. Ho and W. I. Higuchi. J. Pharm. Sci. 63:686–690 (1974).
K. Takada, N. Shibata, H. Yoshimura, H. Yoshikawa, and S. Muranishi. Res. Comm. Chem. Pathol. Pharmacol. 48:12–23 (1985).
C. T. Ueda, M. Lemaire, G. Gsell, and K. Nussbaumer. Biopharm. Drug Disp. 4:113–124 (1983).
J. Grevel. Trans. Proc. 18:9–15 (1986).
I. Komiya, J. Y. Park, A. Kamani, N. F. H. Ho, and W. I. Higuchi. Int. J. Pharm. 4:249–262 (1980).
B. Nashan, J. Bleck, K. Wonigeit, P. Vogt, U. Christians, K.-F. Sewing, T. Beveride, and R. Pichlmayr. Trans. Proc. 20 (Suppl. 2):637–639 (1988).
K. Rommel and R. Bohmer (eds.). Lipid Absorption: Biochemical and Clinical Aspects, University Park Press, Baltimore, Md., 1976, pp. 51–61.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tarr, B.D., Yalkowsky, S.H. Enhanced Intestinal Absorption of Cyclosporine in Rats Through the Reduction of Emulsion Droplet Size. Pharm Res 6, 40–43 (1989). https://doi.org/10.1023/A:1015843517762
Issue Date:
DOI: https://doi.org/10.1023/A:1015843517762