Improved nasal absorption of salmon calcitonin by powdery formulation with N-acetyl- l-cysteine as a mucolytic agent

Abstract

To establish a new formulation technology for the nasal delivery of peptide and protein drugs, we examined whether a mucolytic agent, N-acetyl- l-cysteine (NAC), could enhance the nasal absorption of a powder form of salmon calcitonin, a model peptide drug. We used ethylcellulose as an inert water-insoluble excipient. Various test formulations were prepared, and the effects on nasal absorbability were evaluated in rats and dogs. The powder formulation with NAC gave significant nasal absorption of SCT in both animal models, with absolute bioavailabilities of 30.0% in rats and 24.9% in dogs. Also, nasal administration of this formulation gave a quicker absorption rate than subcutaneous administration of SCT. NAC may reduce nasal fluid viscocity and improve accessibility of the drug to the epithelial membrane. The powder SCT/NAC/ethylcellulose formulation did not induce irritation or histological damage to the nasal membrane in rabbits. These results suggest that this formulation technology may be widely applicable for the nasal delivery of peptide or protein drugs.