A STUDY OF THE COMPLEXATION BETWEEN DANAZOL AND HYDROPHILIC CYCLODEXTRIN DERIVATIVES

Complexation between danazol, a steroid used for endometriosis, and bo th hydroxypropyl-beta-cyclodextrin (HPCD) and sulfobutyl ether-beta-cy clodextrin (SEE) was studied in solution and solid state. Complexation was evaluated in solution using solubility studies and proton magneti c resonance (H-1 NMR) spectroscopy, and in the solid state using x-ray diffraction, Fourier-transform infrared spectroscopy (FTIR), and diss olution studies. Solubility studies suggested the existence of a 1:1 c omplex between danazol and either HPCD or SEE. H-1 MMR showed that com plexation occurs by inclusion of the isoxazole ring of danazol into th e cyclodextrin cavity in both cases. Powder x-ray diffraction indicate d that danazol existed in a crystalline noncomplexed form at low danaz ol-to-cyclodextrin ratios in the coprecipitates prepared by solvent ev aporation method, while at higher ratios danazol existed in an amorpho us completed form. This ratio was 1:10 w/w for HPCD and 1:20 for SBE; the higher ratio in the case of SBE is attributed to early precipitati on of danazol from the solvent used for preparation. FTIR studies show ed that the complexation was accompanied by a shift of the O-H stretch ing of danazol hydroxyl group to a higher frequency, which is attribut ed to the disruption of the intermolecular hydrogen bonding. The disso lution rate of danazol from HPCD coprecipitates was higher than crysta lline danazol in aqueous-isopropanolic medium, while SBE coprecipitate s showed reduced dissolution rates due to the low solubility of SBE in isopropanol. However, SBE coprecipitates showed higher dissolution ra tes in water than in the isopropanolic medium.