Aerosolization and delivery properties of polypeptide microparticles for pulmonary administration of indomethacin

CESCHAN, N; BUCALÁ, V; RAMÍREZ-RIGO, MV; SMYTH, H

Rosario

Congreso; IV Reunión Internacional de Ciencias Farmacéuticas (RICiFa); 2016

Universidad Nacional de Córdoba-Universidad Nacional de Rosario

Indomethacin (IN) is a non-steroidal antiinflamatory drug with acidic groups useful in the treatment of rheumatoid arthritis. However, it possesses important gastrointestinal side effects and low water solubility. The inhalatory route is proposed to deliver this drug avoiding the gastrointestinal effects. In a previous work, IN was combined with the cationic polyelectrolyte polylysine (PL) in aqueous medium. The IN acidic groups have the capability to interact with PL amino groups leading to an ionic complex. The IN-PL solutions were fed in a spray dryer (SD). The relations between SD process parameters and product quality were firstly studied[1]. For the best formulations, microparticles demonstrated to be safer than the pure materials in a cytotoxic assay[2]. Based on these results and in an attempt to improve microparticles biocompatibility, in this work the pH of the SD feed was adjusted to 7. The in vitro deposition and drug release from the obtained microparticles were studied. IN and PL quantities were appropriately selected to obtain the 50% of PL basic groups neutralized. Then, HCl was added to the aqueous IN-PL solutions up to the pH~ 7 was reached. The microparticles were obtained using the SD technology and the operating conditions previously reported[1]. The Emitted (EF), Fine Particle (FPF