Nasal absorption enhancement of 17 beta-estradiol by dimethyl-beta-cyclodextrin in rabbits and rats.

A new formulation for nasal administration containing 17 beta-estradiol (E2) with dimethyl-beta-cyclodextrin (DM beta C) as a solubilizer and absorption enhancer is described. Nasal administration of this E2-DM beta C formulation gave a significantly higher E2 absorption than an E2 suspension in both rabbits and rats. Relative to an intravenous injection of the E2-DM beta C formulation, absolute bioavailabilities of 94.6 and 67.2% were calculated for the nasal E2-DM beta C formulation in rabbits and rats, respectively. Differences in bioavailability may have resulted from differences in experimental animal conditions. The effects on human nasal ciliary activity of the E2-DM beta C formulation were studied with an in vitro method. The formulation was found to exert only a minor effect on ciliary beat frequency. Thus, nasal delivery of E2, using a cyclodextrin inclusion formulation, may have potential for clinical application, e.g., in the therapy of postmenopausal disorders.