Abstract
The solid complex of buserelin acetate (BLA) an agonistic analogue of luteinizing hormonereleasing hormone (LHRH), with heptakis (2, 6-di-O-ethyl)-β-cyclodextrin (DE-β-CyD) was prepared by the kneading method. The in-vitro release of BLA from the arachis oil suspension into the aqueous phase was significantly retarded by the complexation with hydrophobic DE-β-CyD. The oily suspensions can be readily injected subcutaneously into rats using a standard syringe without additives. A single subcutaneous injection of the oily suspension containing the BLA-DE-β-CyD complex at a dose of 1 mg/kg as BLA into rats provided a continuous plasma level of BLA for at least seven weeks, giving a mean residence time of BLA in plasma for the complex about seventy times longer than that for BLA alone. Furthermore, the pharmacological effect of BLA in rats, as indicated by a suppression of plasma testosterone levels to castrate, was sustained for at least one month when the complex was administered. These results support the possible use of DE-β-CyD as an injectable sustained-release type carrier for the chronic treatment of endocrine-dependent diseases with BLA.
