ENHANCEMENT OF NASAL ABSORPTION OF A PEPTIDAL DRUG BY POWDER FORMULATIONS

概要

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Nasal drug delivery, which is a non-invasive route, has been considered as a preferential administration route for peptidal drugs that are usually administered by intravenous injection. Previously, we have demonstrated that the bioavailability of drugs such as leuprolide (M.W. 1, 300) and salmon calcitonin (M.W. 3, 400) can be greatly enhanced by special nasal formulations with powder excipients. In this report, we investigated the nasal absorption of a drug having a slightly higher molecular weight. A peptidal drug with a molecular weight of 5, 500, dalton which is a fragment of the secretory leukocyte protease inhibitor, was nasally administered to rabbits. It was found that the powder formulations with microcrystalline cellulose and hydroxypropyl cellulose enhanced the nasal absorption of the drug to 20 fold in Cmax and 100 fold in bio-availability (i.e., 5%), compared with liquid formulation. Interestingly, the plasma concentration of the drug was kept constant for at least 60 minutes which has not been seen in our previous studies. It was presumed that the protease inhibitory effect of the drug prevented the drug degradation to allow its continuous absorption at the nasal mucosa.
耳鼻咽喉科展望会の論文