Dry powder inhalation (DPI) possesses superiority over nebulizers and pressurized metered-dose inhalers since it keeps the active ingredients in solid state.The key issue involved in DPI is how to increase the drug lung deposition efficiency, especially for the expensive drug with low doses and high efficiency.Many researchers are dedicated to improve drug delivery efficiency by modifying the carrier surface roughness in order to reduce the adhesion force between drug and carrier particles.In our preliminary study, the binary mannitol-chitosan carrier with a nanometered surface roughness can be achieved by one-step spray drying, which exhibits a higher drug pulmonary deposition than the pure mannitol or chitosan due to the proper surface roughness.It proved an efficient and simple way to modify carrier surface topography.However, the DPI performance within such a formulation system is significantly influenced by the drug-carrier ratio, which is related to the saturation of the carrier loading.Therefore, the purpose of this research was to figure out the optimal drug-carrier ratio based on the binary matnitol-chitosan carrier to achieve higher drug delivery efficiency.Spray drying was employed to prepare binary mannitol-chitosan carrier.Budesonide was selected as model drug and micronized to less than 5 um.DPIs were prepared by mixing the binary carriers and micronized budesonide at the ratio of 1∶10, 1∶30and 1∶50 (w/w), respectively.Then the mixture was filled into hard hydroxylpropyl methylcellulose (HPMC) capsules (3 #) at a dose of 10 ± 0.5 mg/cap to evaluate the blend uniformity and drug lung deposition efficiency.Single dose inhaler and apparatus E (next generation impactor, NGI) was used to evaluate the delivery efficiency with commercial Pulmicort Turbuhaler (AstraZeneca AB, 2015-01) as reference under standard conditions (European Pharmacopoeia 7.0).The fine particle fractions (FPF) of Pulmicort Turbuhaler were 34.49 ± 3.9%.While the FPFs for self-made DPIs at different drug-carrier ratio of 1∶10,1∶30 and 1∶50 (w/w) were 41.43 ± 1.8, 32.07 ± 3.04, and 28.60 ± 0.64%, respectively.The drug-carrier ratio exerts significant influence on DPI performance based on the binary mannitol-chitosan carrier with nanometered topography surface.The optimal drug-carrier ratio of 1∶10 for the DPI formulation was better than commercial Pulmicort Turbuhaler regarding to drug pulmonary deposition.