Characterization of polyelectrolyte-atenolol formulation using a nebulized system intended for cardiac targeting

CESCHAN NE; SCIOLI-MONTOTO S; SBARAGLINI ML; RUIZ ME; BUCALA V; RAMIREZ RIGO MV

Córdoba

Congreso; Reunión Internacional de Ciencias Farmacéuticas 2020+1; 2021

Universidad Nacional de Córdoba

Inhalatory delivery allows systemic treatments. In particular, this administration route is being investigated to treat cardiovascular disorders. Inhaled drugs can be administered by using nebulized systems and polyelectrolytes could be useful to develop such nebulized formulations. The aim of this work was to study the in vitro aerosolization and deposition properties of a reconstituted polyelectrolyte-drug formulation and its in vivo performance in a mice model. Atenolol (AT), an antihypertensive and antiarrhythmic drug, was selected as a model drug due to its low oral bioavailability. In order to obtain a stable formulation with adequate geometric size for inhalatory administration, an aqueous dispersion of AT and alginic acid (AA) was spray-dried. AA-AT powder or free AT were redispersed in saline solution and used for in vitro and in vivo assays. The nebulized AAAT system, tested in a multistage impactor, possessed adequate aerodynamic performance: mass median aerodynamic diameter was 3.41microm and around 65% of the formulation would access the lungs. Tests in mice demonstrated that AT from AA-AT was absorbed from lungs to systemic circulation, with plasmatic AUC around 50% higher than the free drug. In conclusion, AA-AT product and the administration technology have potential for cardiac administration of drugs via the lungs.