Amorphous lactose solid dispersion co-spray-dried with magnesium stearate as a novel lactose carrier for dry powder inhalers

초록

PurposeTo overcome the strong inter-particulate interactions between the drug and carrier in dry powder inhalers (DPIs), an amorphous lactose solid dispersion (ALSD) was developed by co-spray drying lactose with magnesium stearate (MgSt) as a novel carrier for fluticasone propionate (FP).MethodsTo investigate the effects of carrier size, morphology, surface properties, and blending time on aerodynamic performance, the ALSD was compared with commercial references: rough-surfaced spherical lactose (SuperTab (R) SD11), tomahawk-shaped lactose (Lactohale (R) 200), and spherical spray-dried lactose, both with and without MgSt. A design of experiments (DoE) approach was employed to optimize the MgSt concentration and blending time.ResultsBased on the DoE results, the optimal MgSt amount was established at 0.2% (w/w), with a blending time design space ranging from 30 to 60 min. Remarkably, the optimized ALSD formulation achieved a fine particle fraction (FPF) of 59.62%. This performance substantially outperformed the reference carriers, exhibiting absolute increases of approximately 25.1 and 41.3% points compared with the FPFs of Lactohale (R) 200 (34.53%) and SuperTab (R) SD11 (18.30%) blended with 0.2% MgSt, respectively.ConclusionThis study demonstrates that while carrier size is a contributing factor, morphology, surface properties, and blending time are critical determinants of aerosolization efficiency. Ultimately, the engineered ALSD successfully mitigates drug-carrier adhesion, markedly improving the aerodynamic performance of FP and representing a highly promising carrier for advanced DPI formulations.

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