Enhanced Bioavailability of Calcitonin Formulated with Alkylglycosides Following Nasal and Ocular Administration in Rats

Abstract

Purpose. The purpose of this study was to characterize the effects of alkylglycosides on the bioavailability of calcitonin following nasal and ocular administration.

Methods. A salmon calcitonin specific radioimmunoassay kit was used to measure calcitonin levels in anesthetized rats at various times after nasal or ocular administration of calcitonin formulated with saline or with octylmaltoside, a medium chain length alkylglycoside or tetradecylmaltoside, a long chain alkylglycoside. The extent of calcitonin absorption was determined directly from the plasma calcitonin level-time curve and the bioavailability of calcitonin was determined from the area under the plasma calcium level-time curve. The calcium level was determined using a colorimetric method.

Results. When the nasal formulation contained calcitonin plus saline or 0.125% octylmaltoside, little or no calcitonin was absorbed. However, plasma calcitonin levels were increased and plasma calcium levels were decreased when the nasal formulation contained calcitonin plus 0.125% or 0.25% tetradecylmaltoside. Maximal calcitonin levels were observed 7.5-10 min after nasal administration of the formulation. Ocular administration of calcitonin formulated with tetradecylmaltoside also resulted in calcitonin absorption, but less calcitonin absorption was found after ocular administration than after nasal administration.

Conclusion. The experimental data indicate that tetradecylmaltoside, but not octylmaltoside, can be effectively used to enhance the bioavailability of nasally and ocularly administered calcitonin.