Abstract
The effect of various cyclodextrins (CD) and cyclodextrin derivatives on indomethacin stability in phosphate buffer, pH 7.4, was investigated. The influence of CD-ring size, type of substituent, degree of substitution, substitution pattern, and influence of CD concentration were monitored. The indomethacin complex in solution was studied by 1H-NMR spectroscopy to develop a molecular inclusion model. The most favorable ring size for the stabilization of indomethacin was the β-CD. The β-CD derivatives inhibited the hydrolysis of indomethacin more effectively than the parent CD. Among the studied CD derivatives, those with lipophilic substituents, such as ethyl or methyl, were superior to those with hydrophilic substitutents. The more hydroxyl groups of the glucose moiety are substituted, the better is the stabilizing effect. Further, the p-chlorobenzoic part of the indomethacin molecule is included in the CD channel.
Similar content being viewed by others
REFERENCES
K. Hartke and E. Mutschler. DAB 9 Kommentar, Wissenschaftl. Verlagsgesellschaft, Stuttgart, 1987, pp. 1974–1981.
M. O. Brian, J. McCauley, and E. Cohen. In K. Florey (ed.), Analytical Profiles of Drug Substances, Academic Press, Orlando, Fla., 1984, pp. 211–238.
S. Goto, W. Tseng, M. Kai, S. Aizawa, and S. Iguchi. Yakuzaigaku 29:42–49 (1969).
H. Krasowska. Acta Pharm. Jugoslav. 24:193–200 (1974).
J. E. Dawson, B. R. Hajratwala, and H. Taylor. J. Pharm. Sci. 66:1259–1263 (1977).
A.-H. Ghanem, H. El-Sabbagh, and H. Abdel-Alim. Pharmazie 34:406–407 (1979).
Y. Hamada, N. Nambu, and T. Nagai. Chem. Pharm. Bull. 23:1205–1211 (1975).
B. W. Müller and U. Brauns. Int. J. Pharm. 26:77–88 (1985).
W. Saenger. Angew. Chem. Int. Edn. Engl. 19:344–362 (1980).
J. Szejtli. Cyclodextrines and Their Inclusion Complexes, Akademiai Kiado, Budapest, 1982, pp. 204–232.
F. Hirayama, M. Kurihara, and K. Uekama. Chem. Pharm. Bull. 34:5093–5101 (1986).
B. W. Müller and U. Brauns. Pharm. Res. 2:309–310 (1985).
Y. Matsui, H. Naruse, K. Mochida, and Y. Date. Bull. Chem. Soc. Jap. 43:1909 (1970).
J. A. Hamilton and M. N. Sabesan. Carbohydr. Res. 102:31–42 (1982).
M. Wiese. FAMILY, unpublished program (1988).
M. Wiese. CHEMPCCS, unpublished program (1988).
M. L. Bender and M. Komiyama. Cyclodextrin Chemistry, Springer-Verlag, Berlin, 1978, pp. 33–64.
J. Pitha, K. Uekama, K. Fukunaga, A. Yoshida, T. Irie, and H. M. Fales. Pharm. Res. 5:713–717 (1988).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Backensfeld, T., Müller, B.W., Wiese, M. et al. Effect of Cyclodextrin Derivatives on Indomethacin Stability in Aqueous Solution. Pharm Res 7, 484–490 (1990). https://doi.org/10.1023/A:1015860531565
Issue Date:
DOI: https://doi.org/10.1023/A:1015860531565