NASAL ABSORPTION OF 17-BETA-ESTRADIOL AND PROGESTERONE FROM A DIMETHYL-CYCLODEXTRIN INCLUSION FORMULATION IN RATS

The nasal absorption of progesterone was studied in male Wistar rats, using dimethyl-β-cyclodextrin (DMßCD) as an absorption enhancer. DMßCD solubilizes steroids which are poorly water soluble by formation of inclusion complexes. Drug preparations with a molar ratio of steroid to DMßCD of 1:2 were used in these experiments. The systemic bioavailabilities of progesterone with DMßCD, and a progesterone suspension were compared. DMßCD increased the bioavailability of progesterone from 18 ± 13% for the suspension to 58 ± 16% for the inclusion complex. The nasal absorption of simultaneously administered estradiol and progesterone with DMßCD as absorption enhancer was also studied, in order to investigate the potential use of this combination in the treatment of postmenopausal disorders. The bioavailabilities of estradiol and progesterone were high, 59 ± 16 and 67 ± 23%, respectively. They were not significantly different from those achieved after separate administration. The combined preparation had only a mild effect on the ciliary beat frequency of human nasal adenoid tissue in vitro. © 1990.