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.
Hermens
W A
WA
Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands.
Deurloo
M J
MJ
Romeyn
S G
SG
Verhoef
J C
JC
Merkus
F W
FW
D000042:Absorption; D000281:Administration, Intranasal; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D003505:Cyclodextrins / Q000494:pharmacology*; D003912:Dextrins / Q000494:pharmacology*; D004355:Drug Stability; D004958:Estradiol / Q000493:pharmacokinetics*; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013213:Starch / Q000494:pharmacology*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D003912:Dextrins; D047392:beta-Cyclodextrins; D004958:Estradiol; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D013213:Starch