Edge activators and a polycationic polymer enhance the formulation of porous voriconazole nanoagglomerate for the use as a dry powder inhaler

Abstract

Purpose: Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1–5 μm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles.

Method: The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size.

Results: Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p < 0.05) with R²=0.95. Small-sized particles were formed (353 nm), while their zeta potential was −30.7 mV. The agglomerates were 2.7 μm in size and their zeta potential was −20.9 mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p < 0.05) and higher fine particle dose (FPD) (p < 0.01), fine particle fraction (FPF) (p < 0.01), and total emitted dose (TED) (p < 0.01) than the pure powder.

Conclusion: The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung.

Keywords:

• Agglomerates
• dry powder aerosol
• lung deposition
• nanoparticles
• voriconazole

Acknowledgements

The authors would like to thank Dr. Heba M. Aboud and Mr. Alfons EZ, Faculty of Pharmacy, Beni-Suef University for their help throughout the study.

Declaration of interest

The authors state that no conflict of interest and have not any received payment in the preparation of this manuscript.