Inhalable Microparticles Embedding Calcium Phosphate Nanoparticles for Heart Targeting: The Formulation Experimental Design

• Main Authors: Bettini, R (Author), Buttini, F (Author), Catalucci, D (Author), Colombo, G (Author), Colombo, P (Author), De Luca, C (Author), Degli Esposti, L (Author), Dotti, A (Author), Iafisco, M (Author), Quarta, E (Author), Rekkas, DM (Author), Rossi, A (Author), Sonvico, F (Author), Trevisi, G (Author), Wong, TW (Author)
• Format: Article
• Language: English
• Published: 2021
• Subjects: calcium phosphate nanoparticles; design of experiment; INHALATION; MANNITOL; microparticles embedding nanoparticles; POWDER; PRODUCT; pulmonary delivery; QUALITY; SPRAY
• Online Access: View Fulltext in Publisher
• DOI: 10.3390/pharmaceutics13111825

Inhalation of Calcium Phosphate nanoparticles (CaPs) has recently unmasked the potential of this nanomedicine for a respiratory lung-to-heart drug delivery targeting the myocardial cells. In this work, we investigated the development of a novel highly respirable dry powder embedding crystalline CaPs. Mannitol was selected as water soluble matrix excipient for constructing respirable dry microparticles by spray drying technique. A Quality by Design approach was applied for understanding the effect of the feed composition and spraying feed rate on typical quality attributes of inhalation powders. The in vitro aerodynamic behaviour of powders was evaluated using a medium resistance device. The inner structure and morphology of generated microparticles were also studied. The 1:4 ratio of CaPs/mannitol led to the generation of hollow microparticles, with the best aerodynamic performance. After microparticle dissolution, the released nanoparticles kept their original size.