The preferred method for measuring aerodynamic particle size distribution (APSD) is cascade impactor. The next generation impactor (NGI) is a relatively new instrument among cascade impactors (CI), which has been included in the pharmacopoeia of various countries, however, there are still many problems in the process of methodology validation due to the cumbersome and complex operation of the method. In this study, the established CI method was systematically validated to reduce the variability of method, which could be used for the quality control of inhalers.

The APSD of ambroxol hydrochloride inhalation solution was determined by NGI, the drug contents at different stages were determined by high performance liquid chromatography (HPLC) method, and aerodynamic statistical parameters were calculated by the CITDS software. The methodology investigation included the establishment of HPLC method, determination of NGI nebulization time, re-entrainment, robustness of flow velocity, inter-stage drug loss, instrument calibration and leakage test, recovery rate, influence of diluent, repeatability and intermediate precision, temperature and humidity, etc.

The adopted HPLC method could be used for the assay of ambroxol hydrochloride; the nebulization time of APSD was determined to be 1 min; the inter-stage drug loss was not greater than 2% of the total nebulized drug amount; the instrument was calibrated and no leakage was detected. The total recoveries were over 95.0%. The source of diluent had no effect on APSD determination results. The established method had good repeatability and intermediate precision. In the laboratory environment (20 ℃~25 ℃) temperature had no effect on the experimental results. Humidity (30% and 50%) had certain influence on the measured results.

NGI was used to establish the method for the determination of APSD of ambroxol hydrochloride inhalation solution, and systematic validation was finished. It was proved that the precision and recovery of the method are good, and the method variability is small, which is suitable for the determination of APSD of ambroxol hydrochloride inhalation solution. This study provided a reference and basis for the establishment and verification of aerodynamic particle size distribution determination, and this method can be used for the quality control of inhaled preparations.