Mucoadhesive microparticles obtained by spray drying for Aatenolol lung delivery

CESCHAN NAZARETH; GARAY AGOSTINA; GALLO LOREANA; BUCALÁ VERÓNICA; MARÍA VERÓNICA RAMIREZ RIGO

Rosario

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas? (RICiFa); 2016

In a previous work, Atenolol (AT, antihypertensive drug with low oral bioavailability) was combined with alginic acid (AA, biocompatible polyelectrolyte) to develop novel dry powder formulations for pulmonary delivery. AT basic groups have the capability to interact with AA acidic groups by ionic interactions, leading to ionic complexes[1]. The new chemical entities were adequate for AT inhalatory administration, even when stored up to 60% of relative humidity for 24 hours[2][3]. As microparticles exhibited good aerosolization performance, it is necessary to study the particle lung residence time and the drug release rate. The aim of this work was to characterize the mucoadhesive and delivery properties of AT-AA microparticles obtained by spray-drying (SD).AT was added to an AA aqueous dispersion to neutralize the 75% of the AA available acidic groups and pH was adjusted to ~7 by adding KOH. The dispersion was fed to a BÜCHI-B-290 spray-dryer. The process yield was determined and microparticles attributes were studied: residual moisture, size, drug released and in vitro mucoadhesion[4].The microparticles displayed low residual moisture (~4.9%), the highest process yield (~85%), the smallest mean volumetric diameter (4µm) and the narrowest particle size distribution compared to SD pure materials. The release experiment (Franz cells) demonstrated that the ionic complex was reversible: after 6 hours, ~85% of the AT (pure or contained in the microparticles) was quantified in the receptor compartment.Maximum detachment force (0.96N) and total detachment work (0.0011J) for the microparticles were significantly higher than the values found for pure AT (p-value<0.05) indicating that the presence of AA would increase the AT residence time in the lung absorption site.In conclusion, the proposed AT-AA system displayed good yield performance (feasibility for larger scale production) and adequate biopharmaceutical properties. These results motivate the next research step of proving the formulation in in vivo models.