The influence of the enhancer dimyristoylphosphatidylglycerol and formulation factors on the nasal absorption of salmon calcitonin

Abstract

The objective of this investigation was to study the effect of the phospholipid dimyristoylphosphatidylglycerol (DMPG) on the intranasal absorption of the polypeptide salmon calcitonin (sCT). DMPG was included as an absorption enhancer for salmon calcitonin in a 0.03 M acetate buffer at pH 4 in a nasal spray formulation. The absorption of sCT was studied as a function of NaCl concentration from 0.045 to 0.3 M. Serum calcitonin was determined using a double-antibody radioimmunoassay (RIA). The presence of the phospholipid demonstrated a significant difference in the intranasal bioavailability of salmon calcitonin. The results showed that DMPG enhanced the nasal absorption of sCT by approximately twofold at a salt concentration of 0.045 M. However, higher salt concentrations in the formulation demonstrated a decrease in the absorption-enhancing effect of DMPG. The effect of DMPG on the calcium-lowering effect of sCT was also studied. There was no significant difference in the hypocalcemic activity of sCT in the presence of DMPG. In addition, it was found that increasing the viscosity of those formulations containing DMPG did not further increase the nasal bioavailability of sCT.