Nivedita Shetty1,2, Heejun Park2, Dmitry Zemlyanov3 & Qi (Tony) Zhou2
1Department of Small Molecule Pharmaceutical Sciences, Genentech, Inc., One DNA Way, South San Francisco, CA 94080
2 Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA
3 Birck Nanotechnology Center, Purdue University, 1205 West State Street, West Lafayette, IN 47907, USA
Summary
Dry powder inhalers (DPI) have been one of the most promising developments in drug delivery systems because powders tend to be more stable than nebulized solution or suspension, do not require propellants and are portable. However, delivering high-dose antibiotics through a DPI is still a challenge. Spray drying is popular for producing DPI formulations as it enables engineering of drug particles; but many spray dried compounds are amorphous in nature and physically unstable. This study aimed to develop dry powder inhaler (DPI) combination formulations of ciprofloxacin and colistin for use in respiratory infections. Effects of colistin on physical stability and aerosolization of spray-dried ciprofloxacin were examined. Our work has shown that recrystallization of amorphous spray dried ciprofloxacin led to significant changes in aerosol performance of DPIs upon storage, which cause critical quality and safety concerns. Our study demonstrated, for the first time, that co-spray drying ciprofloxacin with colistin not only enhances the physical stability of the amorphous powder formulation through intermolecular interactions, but also improves the aerosolization through surface enrichment of colistin. We have successfully incorporated synergistic antibiotics in a single particle which ensures the simultaneous delivery of combinations to the same infection sites, potentially maximizing antimicrobial synergy.
Key Message
This study provides a fundamental understanding in storage-induced physical and aerosol instability of the spray dried powder formulations. Also, it offers novel strategies to tackle both the multi-drug resistant problem and physical stability issue of spray dried formulations by combining two synergistic antibiotics into a single formulation.