THE POTENTIAL OF CYCLODEXTRINS AS ABSORPTION ENHANCERS IN NASAL DELIVERY OF PEPTIDE DRUGS

The potential of cyclodextrins, in particular dimethyl-beta-cyclodextr in (DM beta CD), as absorption enhancers was investigated for the nasa l absorption of two peptide drugs: an ACTH(4-9) hexapeptide analogue a nd the polypeptide hormone, insulin. Studies in rats showed that DM be ta CD largely improved the absorption of both peptide drugs, resulting in bioavailabilities of 70 to 100%. The effective DM beta CD concentr ation was in the order of 2% (w/v), and the increased permeability of the rat nasal epithelium as caused by DM beta CD returned to normal ph ysiological conditions in time. On the contrary, insulin/DM beta CD so lutions were ineffective in enhancing nasal insulin absorption in rabb its and men, whereas a small absorption enhancement was observed for t he small ACTH(4-9) analogue in rabbits. Thus substantial interspecies differences appear to exist in the absorption of peptide drugs with DM beta CD as enhancer. Nonetheless, studies in rabbits demonstrated tha t insulin/DM beta CD powder formulations were much more effective than liquid preparations. The nasal insulin bioavailability was in the ord er of 13% for the insulin/DM beta CD powder, and negligible for both a control insulin/lactose powder and insulin/DM beta CD liquid formulat ions. In conclusion, the cyclodextrin derivative DM beta CD is a poten t enhancer of nasal peptide absorption. The efficacy of DM beta CD, ho wever, differs largely between species and is also greatly dependent u pon the nasal dosage form.