Pulmonary absorption enhancement of salmon calcitonin

The aim of this work was to develop formulations of calcitonin for pulmonary delivery to enhance the absorption and study the comparative pharmacodynamic behavior of developed formulations in rats. Formulations with different pH, absorption promoters of different classes and combination thereof at three concentration levels were prepared and instilled intratracheally in anesthetized rats. The absorption of calcitonin was measured by its hypocalcemic effect in blood collected at specific time points. The formulations having least concentration of absorption promoter with significant blood calcium reduction were selected out from three concentration levels of absorption promoters used. The relative pulmonary bioactivity of calcitonin in acetate buffer pH 6.0 and pH 3.9 was 21.0+/-1.5% and 53.9+/-2.8%, respectively, compared to subcutaneously administered calcitonin in equivalent dose. When sodium tauroglycocholate, dimethyl beta-cyclodextrin, chymostatin, and bacitracin were co-administered in acetate buffer pH 3.9 solution, the relative bioactivity of 139.1+/-7.3% was obtained. Only 72.0+/-2.7%, 79.2+/-3.9%, 83.0+/-2.1% and 87.0+/-3.9% were obtained, respectively, upon incorporation of these absorption promoters individually. It was concluded that absorption promoters in combination significantly increase the pulmonary bioactivity of calcitonin. These studies proves that calcitonin administered through the pulmonary route can yield higher systemic absorption for enhanced bioactivity.