title: Antidiuretic effect of desmopressin chimera agglomerates by nasal administration in rats.
abstract: In the present study, a nasal powder of the antidiuretic peptide desmopressin (DDAVP) formulated as chimera agglomerates was studied to improve drug bioavailability and provide a flexible drug product. Firstly, DDAVP was spray-dried along with mannitol and lecithin to produce primary microparticles capable of instantaneous dissolution in water. The chimera agglomerates were spontaneously formed by mechanically vibrating the microparticles on two stacked sieves. Agglomerate formation and strength were favored by the presence of lecithin. Drug content and dissolution rate remained unmodified after agglomeration. However, owing to the agglomerate larger size, powder flowability was greatly improved in comparison with the original microparticles, allowing accurate powder dosing into the nasal delivery device. DDAVP in vitro permeation across excised rabbit nasal mucosa from the agglomerates was significantly higher than that obtained from a commercial liquid nasal spray. In rats, intranasal DDAVP agglomerates allowed for efficient administration with almost 80% of the loaded powder emitted from the device into the animal nose. The administration of DDAVP agglomerates induced a significant reduction in urine production. Moreover, the antidiuretic effect of agglomerates did not significantly differ from the one induced by an intravenous injection of DDAVP at a ten-fold lower dose.
authors.affiliation: Department of Pharmaceutical Sciences, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
authors.forename: Anna Giulia
authors.initials: AG
authors.lastname: Balducci
authors.forename: Luca
authors.initials: L
authors.lastname: Ferraro
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bortolotti
authors.forename: Claudio
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: Paolo
authors.initials: P
authors.lastname: Colombo
authors.forename: Fabio
authors.initials: F
authors.lastname: Sonvico
authors.forename: Paola
authors.initials: P
authors.lastname: Russo
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
mesh_terms: D000281:Administration, Intranasal; D061605:Administration, Intravenous; D000818:Animals; D050034:Antidiuretic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects; D010316:Particle Size; D011208:Powders / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology / Q000706:statistics & numerical data; D012995:Solubility
chemical_list: D050034:Antidiuretic Agents; D011208:Powders; D003894:Deamino Arginine Vasopressin