Lecithin-based modified soft agglomerate composite microparticles for inhalable montelukast: Development, tolerability and pharmacodynamic activity

Abstract In this work, montelukast (MTK) was incorporated in inhalable soft agglomerates (SA) exhibiting inherent characteristics for deep lung deposition while expressing good flowability and enhanced shelf-life stability. Mannitol and ovalbumin were used as particle shapers and lecithin as binder during microparticles (MPs) preparation by spray drying. The spontaneously agglomerated MPs with an adhesive surface were designed to deagglomerate under the effect of aerosolization with selected dry powder inhaler device, achieving satisfactory lung deposition. A pharmacodynamic study was also undertaken to evaluate MTK-SA effectiveness in asthmatic rats. Optimized SA showed agglomerated small MPs capable of dispersing into individual particles under pressures exceeding 1Bar. They exhibited high respirable fraction of ˃54% and were able to release MTK in >15 min. MTK-SA, delivered by pulmonary insufflation, was able to equally reduce the inflammatory response in asthmatic rats at a ten fold lower dose compared to oral tablet.