Methylated β-cyclodextrins are able to improve the nasal absorption of salmon calcitonin

Abstract

The absorption enhancing effect of methylated β-cyclodextrins on the 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 largely improved by coadministration of cyclodextrins as apparent from the effect on serum calcium concentrations. Trimethyl-β-cyclodextrin (TMβCD), at a concentration of 5% (w/v), was the least potent enhancer. Randomly methylated-β-cyclodextrin (RMβCD) and dimethyl-β-cyclodextrin (DMβCD), all at a concentration of 5% (w/v), were almost equally effective in decreasing serum calcium levels, and the hypocalcemic responses were similar to those of i.v. and s.c. injected sCT. Absorption enhancement was already achieved with 1% DMβCD added to the nasal formulations. In rabbits, only the effect of DMβCD on the nasal sCT absorption was investigated. A total serum calcium decrement in 4 hours of 9.4±3.9% (mean±SD) was observed following nasal administration of 12.6 IU/kg sCT with 5% DMβCD, comparable to that of i.v.-injected sCT. In conclusion, the methylated cyclodextrins DMβCD and RMβCD are suitable absorption enhancers for nasal sCT administration, which is expected to have a clinical impact on the therapy with calcitonin.