Exploring the potential influence of drug charge on downstream deposition behaviour of DPI powders
International Journal of Pharmaceutics(2020)
摘要
Dry powder inhaler (DPI) development is limited by the time- and labor-consuming in vitro lung deposition test. It's highly desirable to find an easy tool for DPI formulation screening. Dynamic powder rheological properties seem to present many advantages, however, the adoptability needs to be verified. Drug charge is an important parameter especially for DPI formulation design but how it affects the process of pulmonary drug delivery is unavailable. Therefore, the objective of this study is to explore the influence of drug charge on DPI powders, further testing the potentials of powder properties for downstream deposition behavior prediction. Taking five differently charged drugs as model, influence of drug charge on uniformity, rheological and aerodynamic properties of the mixtures were investigated systemically. It was found that mometasone furoate with near neutral charge presented better content homogeneity, while significantly decreased recovery was noted for charged drugs, such as positively charged drug (salbutamol sulphate and indacaterol maleate) mixtures and negatively charged drug (budesonide and fluticasone propionate) mixtures. Moreover, drug charge also influenced flowability and cohesion of their admixture with lactose. As for the downstream deposition, neutral drugs presented higher fine particle fraction (FPF), followed by positively charged drugs and negatively charged drugs. Good correlations between basic flowability energy, aeration energy, Permeability and FPF were established irrespective of different drugs. Principal component analysis results suggested flowability had a greater influence on FPF when mixtures were less cohesive. In conclusion, this study demonstrated drug charge can influence physicochemical, rheological and aerodynamic properties of the admixture, and DPIs' dynamic properties could be used as potential tools to predict downstream deposition with good accuracy.
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关键词
Drug charge,Dry powder inhaler (DPI),Dynamic powder properties,Downstream deposition
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