Influence of Various Cyclodextrins on the Stability of Hydrocortisone 17-Butyrate in Aqueous Solution

• Published in: Archives of pharmacal research Vol. 15; no. 2; pp. 176 - 183
• Main Authors: Chun, In-Koo, Kim, Bo-Young
• Format: Journal Article
• Language: Korean
• Published: 1992
• Subjects: Stabilization; Ionic strength; Hydrocortisone butyrate; Cyclodextrins; pH effect; Stability constant; Solvent; Inclusion complex; Rearrangement
• ISSN: 0253-6269; 1976-3786

The stabilizing effects of $\alpha$-$\beta$-$\gamma$- and dimethyl-$\beta$-cyclodextrins $(\alpha$-, $\beta$-, $\gamma$- and DM-$\beta-$-CyDs) on the degradation of hydrocortisone 17-butyrate (HC-17B) in aqueous solution was investigated. Hc-17B underwent a facile hydroxide ion-catalyzed rearrangement to the less active 21-butyrate ester by the apparent first-order kinetics, and maximum stability of HC-17B was obtained at around pH 4.0. The stability of HC-17B was increased by inclusion complexation with $\alpha$-, $\gamma$- and DM-$\beta$-CyD in the pH range of 2.0-8.0 examined, whereas $\beta$-CyD accelerated the degradation of HC-17B at the pH higher than 5.0. The effects of ionic strength, solvent, temperature and CyD concentration were also investigated. Stability constants and apparent degradation rate constants of HC-17B-$\gamma$-CyD and HC-17B-DM-$\beta$-CyD complexes were determined kinetically on the basis of 1:1 complexation. The results suggested that the inclusion complexation with $\gamma$-CyD or DM-$\beta$-CyD was most useful means to enhance the stability of the steroid.