Indomethacin microparticles for inhalatory administration using spray-drying equipment

CESCHAN NE; GALLO LC; BUCALÁ V; RAMIREZ RIGO MV

Londres

Workshop; 7th International Granulation Workshop; 2015

University of Sheffield

Indomethacin (IN) is a non-steroidal antiinflammatory drug, which is an interesting candidate for being administered by an alternative route due to its gastrolesive and oral bioavailability problems. An inhalatory drug delivery system containing IN could be useful for both local and systemic treatments of rheumatoid arthritis and its pulmonary complications. Microparticles based on an IN and polylysine (PL, a biocompatible cationic polymer) were obtained by spray drying (SD) with adequate yields for a lab scale equipment. The aim of this work is to characterize the particulate product in order to determine its applicability for pulmonary drug targeting. The SD operating conditions were selected based on a previous work. Several formulations, varying the relative composition IN/polymer and the total solid content of the feed solutions, were tested. Product properties (crystallinity, density, morphology and particle size distribution by laser diffraction (LD) and using a next generation impactor) and the IN- PL ionic interaction (assessed by FT-infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) and thermal analysis) were studied. The ionic interaction between the IN and PL was proved by FT-IR. The powder was amorphous and this state was found to be stable for nine months of storage.The SD particles were rounded, smooth and exhibited some holes. Particular attention was focused on the particle size distribution to evaluate the feasibility of employing the powder for pulmonary deposition. The aerodynamic diameter distribution obtained with the next generation impactor showed that the powders presented a high respirable fraction, being then adequate for the inhalatory administration of IN. By comparing this data with the information obtained by LD technique, it was found that LD can be used to preliminary evaluate the aerodynamic diameters and then to assess the particles deposition pattern.