Carrier based dry powder inhalers (DPIs) have become a hotspot in recent years. Lactose is the most commonly used carrier in DPI, while its further application was hindered by its hygroscopicity. Agglomeration induced by hygroscopicity would cause the deterioration of aerosolization performance. In this study, cyclodextrin-lactose binary carriers (CLBCs) were produced by spray-drying so as to surmount the hygroscopicity. Physicochemical attributes of CLBCs were explored in detail. Hygroscopicity of CLBCs was elucidated by dynamic vapor sorption study. Aerosolization performance of its corresponding DPIs was evaluated by the next generation impactor (NGI). In addition, the preliminary reserach on the formation mechanism of CLBCs was carried out. The optimal formulation of CLBC (L-3) was proven to possess anti-hygroscopicity and aerosolization performance enhancement properties. To be concise, the moisture uptake of L-3 was ca 2.8% which was far lower than spraydriedlactose (L-0, ca. 50.1%). L-3 exhibited a high fine particle fraction value of 59.16 +/- 1.41 and it was 3.7-fold against L-0 After 10-day storage in high humidity, L-3 maintained its physicochemical properties and the superior aerosolization performance. It was proved that CLBC with anti-hygroscopicity and aerosolization performance enhancement properties was a promising approach for pulmonary drug delivery, which could provide new possibilities to the application of hygroscopic carriers for DPI. (C) 2018 Published by Elsevier B.V.