CONTROLLED-RELEASE OF THE LHRH AGONIST BUSERELIN ACETATE FROM INJECTABLE SUSPENSIONS CONTAINING TRIACETYLATED CYCLODEXTRINS IN AN OIL VEHICLE

Heptakis(2,3,6-tri-O-acetyl)-beta-cyclodextrin (TA-beta-CyD) and octakis(2,3,6-tri-O-acetyl)-gamma-cyclodextrin (TA-gamma-CyD) were prepared for use as hydrophobic carriers of buserelin acetate (BLA),an agonist of luteinizing hormone releasing hormone. The results from this study suggest that the in vitro release of BLA from the peanut oil suspension into the aqueous phase was retarded by complexation with TA-CyDs. A single subcutaneous injection of the oily suspension of BLA containing TA-beta-CyD and TA-gamma-CyD in rats led to retardation of plasma levels of BLA, resulting in 25- and 39-fold longer mean residence times, respectively, than that of BLA alone. Simultaneously with the suppression of plasma testosterone to castrate level, the pharmacological effectiveness of BLA continued for 1-2 weeks and significant weight reduction of genital organs was observed due to the antigonadal effect. Since TA-beta-CyD and TA-gamma-CyD were degraded enzymatically in rat skin homogenates, both TA-CyDs can be useful as bioabsorbable sustained-release carriers for hydrophilic peptides following the subcutaneous injection of an oily suspension.