METHYLATED BETA-CYCLODEXTRINS ARE ABLE TO IMPROVE THE NASAL ABSORPTION OF SALMON-CALCITONIN

The absorption enhancing effect of methylated beta-cyclodextrins on th e nasal absorption of salmon calcitonin (sCT) was studied in rats and rabbits. The nasal absorption of sCT following administration without additives was low in both species. The absorption in rats could be lar gely improved by coadministration of cyclodextrins as apparent from th e effect on serum calcium concentrations. Trimethyl-beta-cyclodextrin (TM beta CD), at a concentration of 5% (w/v), was the least potent enh ancer. Randomly methylated-beta-cyclodextrin (RM beta CD) and dimethyl -beta-cyclodextrin (DM beta CD), all at a concentration of 5% (w/v), w ere almost equally effective in decreasing serum calcium levels, and t he hypocalcemic responses were similar to those of i.v. and s.c. injec ted sCT. Absorption enhancement was already achieved with 1% DM beta C D added to the nasal formulations. In rabbits, only the effect of DM b eta CD on the nasal sCT absorption was investigated. A total serum cal cium decrement in 4 hours of 9.4 +/- 3.9% (mean +/- SD) was observed f ollowing nasal administration of 12.6 IU/kg sCT with 5% DM beta CD, co mparable to that of i.v.-injected sCT. In conclusion, the methylated c yclodextrins DM beta CD and RM beta CD are suitable absorption enhance rs for nasal sCT administration, which is expected to have a clinical impact on the therapy with calcitonin.