The potential of cyclodextrins as absorption enhancers in nasal delivery of peptide drugs

• Published in: Journal of controlled release Vol. 29; no. 3; pp. 351 - 360
• Main Authors: Verhoef, J.Coos, Schipper, Nicolaas G.M., Romeijn, Stefan G., Merkus, Frans W.H.M.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.1994; Elsevier
• Subjects: Absorption enhancement; Biological and medical sciences; Cyclodextrin; Dosage form; General pharmacology; Interspecies difference; Medical sciences; Nasal delivery; Peptide drug; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Dosage form; Interspecies difference; Cyclodextrin; Absorption enhancement; Nasal delivery; Peptide drug
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/0168-3659(94)90080-9

The potential of cyclodextrins, in particular dimethyl-β-cyclodextrin (DMβCD), as absorption enhancers was investigated for the nasal absorption of two peptide drugs: an ACTH (4–9) hexapeptide analogue and the polypeptide hormone, insulin. Studies in rats showed that DMβCD largely improved the absorption of both peptide drugs, resulting in bioavailabilities of 70 to 100%. The effective DMβCD concentration was in the order of 2% (w/v), and the increased permeability of the rat nasal epithelium as caused by DMβCD returned to normal physiological conditions in time. On the contrary, insulin/DMβCD solutions were ineffective in enhancing nasal insulin absorption in rabbits and men, whereas a small absorption enhancement was observed for the small ACTH (4–9) analogue in rabbits. Thus substantial interspecies differences appear to exist in the absorption of peptide drugs with DMβCD as enhancer. Nonetheless, studies in rabbits demonstrated that insulin/DMβCD powder formulations were much more effective than liquid preparations. The nasal insulin bioavailability was in the order of 13% for the insulin/DMβCD powder, and negligible for both a control insulin/lactose powder and insulin/DMβCD liquid formulations. In conclusion, the cyclodextrin derivative DMβCD is a potent enhancer of nasal peptide absorption. The efficacy of DMβCD, however, differs largely between species and is also greatly dependent upon the nasal dosage form.