Nasal powders for delivery of disease modifying agents in early treatment of Alzheimer’s disease: formulation and characterization

The research conducted during this Ph.D. led to the development of a first prototype of a 2-drug powder formulation for nasal delivery with interesting features for the management of Alzheimer’s disease. First of all, the study proposed a flurbiprofen powder with suitable characteristics for nasal administration and nose-to-brain targeting. The powder comprised spray-dried flurbiprofen sodium microparticles, fast dissolving and sustaining extensive drug transport ex vivo across a model tissue of nasal mucosa. The construction of the final nasal dosage form continued through the agglomeration of the flurbiprofen microparticles with spray-dried excipient microparticles. In a rat animal model both flurbiprofen microparticles and agglomerates allowed for the drug to enter the central nervous system and enhanced its brain disposition compared to systemic drug administration by intravenous injection. The combination of flurbiprofen spray-dried microparticles with a second drug in powder form was the next step to better address Alzheimer’s disease by the so-called “multi-target approach”. To this purpose, insulin spray-dried microparticles were studied and combined with flurbiprofen ones in form of agglomerates for nasal delivery.