Abstract
Inclusion complexation of nocloprost, a potent antiulcer prostaglandin derivative, with α-, β-, and γ-cyclodextrins (CyDs) in aqueous solutions has been studied by the solubility method and13C-NMR spectroscopy. The steric requirement of host-guest interaction was reflected in the magnitude of the stability constants and the thermodynamic parameters of the inclusion complexes. Solid complexes of nocloprost with β- and γ-CyDs in a molar ratio of 1 : 2 were obtained on the basis of aBs-type phase solubility diagram. The X-ray diffraction data suggested that nocloprost is included in the cylindrical channel formed by coaxial alignment of γ-CyD molecules to give a channel type structure. Release and thermal behavior of the solid complexes was examined and compared with nocloprost itself. The results indicated that the β-CyD complex may have great utility among the three CyDs, being a rapid dissolving form of nocloprost with improved thermal stability.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
J. Szejtli:Cyclodextrins and their Inclusion Complexes, Akadémiai Kiadó, Budapest (1982).
D.Duchêne (ed.):Cyclodextrins and their Industrial Uses, Editions de Santé, Paris (1987).
W. Saenger:Angew. Chem. Int. Ed. Engl. 19, 344 (1980).
K. Uekama and M. Otagiri:CRC Critical Reviews in Therapeutic Drug Carrier Systems 3, 1987, pp. 1–40.
K. Uekama, F. Hirayama, Y. Yamada, K. Inaba, and K. Ikeda:J. Pharm. Sci. 68, 1059 (1979).
K. Uekama, F. Hirayama, A. Fujise, M. Otagiri, K. Inaba, and H. Saito:J. Pharm. Sci. 73, 382 (1984).
K. Uekama, A. Fujise, F. Hirayama, M. Otagiri, and K. Inaba:Chem. Pharm. Bull. 32, 275 (1984).
F. A. Fitzpatrick:Anal. Chem. 48, 499 (1976).
T. Higuchi and K. A. Connors:Adv. Anal. Chem. Inst. 4, 117 (1965).
H. Nogami, T. Nagai, and A. Suzuki:Chem. Pharm. Bull. 14, 329 (1966).
M. L. Bender and M. Komiyama:Cyclodextrin Chemistry, Springer-Verlag, Berlin (1978).
J. E. Leffler and E. Grunwald:Rates and Equilibria of Organic Reactions, John Wiley & Sons, Inc., New York (1963).
E. A. Lewis and L. D. Hansen:J. Chem. Soc. Perkin Trans. 2, 2081 (1973).
G. F. Cooper and J. Fried:Proc. Nat. Acad. Sci. USA. 70, 1579 (1973).
W. W. Conover and J. Fried:Proc. Nat. Acad. Sci. USA. 71, 2157 (1974).
K. Uekama and F. Hirayama:Chem. Pharm. Bull. 26, 1195 (1978).
F. Hirayama, K. Uekama, and H. Koinuma:Chem. Pharm. Bull. 28, 1975 (1980).
J. W. Edmonds and W. L. Duax:J. Am. Chem. Soc. 97, 413 (1975).
K. Takeo and T. Kuge: Agri. Biol. Chem.34, 568 (1970).
K. Uekama, F. Hirayama, H. Tanaka, and K. Takematsu: Chem. Pharm. Bull.26, 3779 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kurihara, M., Hirayama, F., Uekama, K. et al. Improvement of some pharmaceutical properties of nocloprost by β- and γ-Cyclodextrin Complexation. J Incl Phenom Macrocycl Chem 8, 363–373 (1990). https://doi.org/10.1007/BF01041192
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01041192