Effect of powder properties on the aerosolization performance of nanoporous mannitol particles as dry powder inhalation carriers

Abstract

ABSTRACT Carrier based dry powder inhalers (DPIs) are common vehicles for pulmonary delivery of active pharmaceutical ingredients (APIs), thus powder properties of carrier would generate a pronounced impact on the two dominant delivery stages of the DPIs. In our previous study, a novel modified carrier, the nanoporous mannitol carriers (NPMCs) was prepared to achieve satisfactory aerosolization performance. While the aerosolization performance enhancement mechanism of NPMCs based DPI was still uncovered. The purpose of this study was to explore the relationship between the powder property of NPMCs and the aerosolization performance of their corresponding DPI formulations. Particle size analysis of NPMCs was assessed by Sympatec® dynamic laser diffraction. Powder property of NPMCs was performed by FT4 powder rheometer. Aerosolization performance was evaluated by the next generation impactor to simulate the deposition profile of NPMCs based DPI formulations in respiratory tract. Similar particle size distribution was observed among the NPMCs formulations (p > 0.05), which were appropriate for DPIs. And NPMCs exhibited superior flowability, aeration and permeability behaviors in FT4 tests, meanwhile higher fine particle fraction (FPF) values in NGI test comparing to the nonporous mannitol. Further, two positive correlations between the basic flow energy (BFE) and ρb (R2 = 0.901), specific energy and ρb values (R2 = 0.912) were obtained in NPMC systems, respectively. The relationship between BFE and FPF was explored quantitatively as well, and it revealed an inverse correlation (R2 = 0.934). Therefore, the aerosolization performance enhancement of NPMCs based DPI could be reasonably explained by powder property of carriers quantified by the FT4 powder rheometer, which was a promising tool for the design of DPI carrier.