Abstract
A new formulation for nasal administration containing 17β-estradiol (E2) with dimethyl-β-cyclodextrin (DMβC) as a solubilizer and absorption enhancer is described. Nasal administration of this E2-DMβC formulation gave a significantly higher E2 absorption than an E2 suspension in both rabbits and rats. Relative to an intravenous injection of the E2-DMβC formulation, absolute bioavailabilities of 94.6 and 67.2% were calculated for the nasal E2-DMβC 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-DMβC 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.
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REFERENCES
R. L. Young and J. W. Goldzieher. Drugs 33:95–106 (1987).
R. W. Lievertz. Am. J. Obstet. Gynecol. 156:1289–1293 (1987).
Y. W. Chien. Transnasal Systemic Medications. Fundamentals, Developmental Concepts and Biomedical Assessments, Elsevier, Amsterdam, 1985.
L. A. Rigg, B. Milanes, B. Villanueva, and S. S. C. Yen. J. Clin. Endocrinol. Metab. 45:1261–1264 (1977).
L. Ohman, R. Hahnenberger, and E. D. B. Johansson. Contraception 22:349–385 (1980).
A. Mirimanoff and A. Palley. Pharm. Acta Helv. 41:25–38 (1966).
A. D. Barton and R. V. Lourenço. Arch. Intern. Med. 131:140–144 (1973).
R. N. Bawarshi-Nassar, A. A. Hussain, and P. A. Crooks. Drug Metab. Dispos. 17:248–254 (1989).
K. Uekama and M. Otagiri. CRC Crit. Rev. Ther. Drug. Car. Syst. 3:1–40 (1986).
M. Nógrádi. Drugs Future 9:577–578 (1984).
G. S. M. J. E. Duchateau, K. Graamans, J. Zuidema, and F. W. H. M. Merkus. Laryngoscope 95:854–859 (1985).
W. A. J. J. Hermens and F. W. H. M. Merkus. Pharm. Res. 4:445–449 (1987).
T. Higuchi and K. A. Conners. Adv. Anal. Chem. Instrum. 4:117–212 (1965).
A. S. Harris, M. Ohlin, E. Svensson, S. Lethagen, and I. M. Nilsson. J. Pharm. Sci. 78:470–471 (1989).
A. N. Fisher, K. Brown, S. S. Davis, G. D. Parr, and D. A. Smith. J. Pharm. Pharmacol. 37:38–41 (1985).
M. J. M. Deurloo, W. A. J. J. Hermens, S. G. Romeyn, J. C. Verhoef, and F. W. H. M. Merkus. Pharm. Res. 6:853–856 (1989).
H. J. M. van de Donk, J. Zuidema, and F. W. H. M. Merkus. Rhinology 18:93–104 (1980).
E. B. Brittebo. Acta Pharmacol. Toxicol. 57:285–290 (1985).
C. J. Reed, E. A. Lock, and F. De Matteis. Biochem. J. 240:585–592 (1986).
J. Pitha, S. M. Harman, and M. E. Michel. J. Pharm. Sci. 75:165–167 (1986).
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Hermens, W.A.J.J., Deurloo, M.J.M., Romeyn, S.G. et al. Nasal Absorption Enhancement of 17β-Estradiol by Dimethyl-β-Cyclodextrin in Rabbits and Rats. Pharm Res 7, 500–503 (1990). https://doi.org/10.1023/A:1015816716544
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DOI: https://doi.org/10.1023/A:1015816716544