The potential of cyclodextrins as absorption enhancers in nasal delivery of peptide drugs
Verhoef, J.C.; Schipper, N.G.M.; Romeijn, S.G.; Merkus, F.W.H.M.
Journal of Controlled Release 29(3): 351-360
ISSN/ISBN: 0168-3659 DOI: 10.1016/0168-3659(94)90080-9
The potential of cyclodextrins, in particular dimethyl--cyclodextrin (DMCD), 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 DMCD largely improved the absorption of both peptide drugs, resulting in bioavailabilities of 70 to 100%. The effective DMCD concentration was in the order of 2% (w/v), and the increased permeability of the rat nasal epithelium as caused by DMCD returned to normal physiological conditions in time. On the contrary, insulin/DMCD 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 DMCD as enhancer. Nonetheless, studies in rabbits demonstrated that insulin/DMCD powder formulations were much more effective than liquid preparations. The nasal insulin bioavailability was in the order of 13% for the insulin/DMCD powder, and negligible for both a control insulin/lactose powder and insulin/DMCD liquid formulations. In conclusion, the cyclodextrin derivative DMCD is a potent enhancer of nasal peptide absorption. The efficacy of DMCD, however, differs largely between species and is also greatly dependent upon the nasal dosage form.