Systematic aging of degradable nanosuspension ameliorates vibrating-mesh nebulizer performance.

CONTEXT: The process of vibrating-mesh nebulization is affected by sample physicochemical properties. Exemplary, electrolyte supplementation of diverse formulations facilitated the delivery of adequate aerosols for deep lung deposition. OBJECTIVE: This study addressed the impact of storage conditions of poly(lactide-co-glycolide) nanosuspension on aerosol properties when nebulized by the eFlow®rapid. MATERIALS AND METHODS: First, purified nanosuspensions were supplemented with electrolytes (i.e. sodium chloride, lactic and glycolic acid). Second, the degradable nanoparticles (NP) were incubated at different temperatures (i.e. 4, 22 and 36 °C) for up to two weeks. The effect of formulation supplementation and storage on aerosol characteristics was studied by laser diffraction and correlated with the sample conductivity. RESULTS AND DISCUSSION: Nebulization of purified nanosuspensions resulted in droplet diameters of >7.0 µm. However, electrolyte supplementation and storage, which led to an increase in sample conductivity (>10-20 µS/cm), were capable of providing smaller droplet diameters during vibrating-mesh nebulization (≤5.0 µm). No relevant change of NP properties (i.e. size, morphology, remaining mass and molecular weight of the employed polymer) was observed when incubated at 22 °C for two weeks. CONCLUSION: Sample aging is an alternative to electrolyte supplementation in order to ameliorate the aerosol characteristics of degradable NP formulations when nebulized by vibrating-mesh technology.