Development and characterization of nanodispersion-based sildenafil pressurized metered-dose inhaler using combined small-angle X-ray scattering, dynamic light scattering, and impactors

Abstract

The objectives of this study were to develop and measure the hydrodynamic particle size of sildenafil citrate nanoparticles dispersed in a pressurized metered-dose inhaler (pMDI) using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Aerodynamic properties and charges of aerosolized particles after emission from the pMDI were monitored by next generation impactor (NGI) and electrical low pressure impactor (ELPI). Nanodispersion-based sildenafil citrate pMDI formulated with 0, 1, 5 and 10% poloxamer 188 (P188) as a surfactant namely formulations F1, F2, F3 and F4, respectively. The results showed no precipitated or crystal growth during 6 months. The particle size and polydispersity index of the F3 obtained from the DLS analysis were 9.0 ± 1.6 d nm and 0.421 ± 0.038, respectively. The respective characteristics obtained from the SAXS data were 5.2 ± 1.2 d nm. The results from SAXS were smaller than those obtained from DLS. Larger hydrodynamic shell contributed to the larger size of nanoparticles. The sildenafil citrate content of pMDI was 107–109.5% LA. The mass median aerodynamic diameter (MMAD) from NGI was 1.2–2 μm and the fine particle fraction was 60%. The formulation without P188 (F1) showed particles of 10–100 nm and 0.1–1 μm and exhibited a unipolar charge profile. The formulations with P188 exhibited a bipolar charge profile with the nano-size of 200 (F3) and 300–800 nm (F4). The formulations of pMDI exhibited either a unipolar charge or bipolar charge profile depending on the composition of the formulation. The sildenafil citrate pMDI with 5% P188 generated sub-micronized and nano-sized aerosols with bipolar charged particles. The DLS and SAXS techniques were alternative ways to determine the particle size and size distribution of the pMDI products. The EPLI is also suitable to assess the stability of the MDI products from charge measurement.