Preparation And Evaluation Of Dry Powder Inhalation Of Extract Of Trollius Chinesis Bungle

Objective: To prepare dry powder inhalation with extract of Trollius chinesis bungle and to evaluate the DPI's physicochemical and in vitro safety properties.Methods: (1) The evaluation methods of DPI were established, which include HPLC determination method with a target compound of orentin, aerosolisation performances and dissolution properties of DPI. (2) DPI was prepared by mixing micronized ETB and coarse lactose carrier homogeneously. Spray drying was employed to prepare micronized ETB, formulation and preparing process were optimized through aerosolisation performances. The lactose carrier was optimized through univariate design. After DPI formed, the aerosolisation performances were determined. (3) The formulations were incorporated with frequently-used pharmaceutical excipient to obtain DPI with desired properties. (4) A549 cell was employed to evaluate the safety issue of materials used in DPI formulation with MTT method.Results: (1) The in vitro determination method of orentin was stable and reliable; all the other methods were easy to operate and able to show properties of DPI prepared in all respects. (2) Spray drying was a feasible way to prepare micronized ETB with controllable parameters, the optimized method for micronized TEB preparation was: ethanol concentration 50%, feed concentration 50% (W/V), inlet temperature 80℃, aspirator efficiency 100%, pump rate 7.5 mL·min^-1. Particles size of micronized ETB distributed from 1 to 20μm, the fine particles fraction and emitted dose was (10.7±1.7) % and (75.3±21.1) %, respectively. The aerosolisation performances of resulted DPI were good, which fine particles fraction was (56.4±2.2) % and emitted dose was (95.9±3.0) %. (3) Ammonium carbonate significantly increase the particles size, and improved flowability and dissolution properties of micronized ETB. Gelatin and PVP K30 enhanced the dissolution rate. However, PVP K30 decreased aerosolisation performances significantly. Chitosan and HPMC K4M were chosen to prepare bio-adhesive micronized ETB. Chitosan had no significant influences on DPI properties. HPLC K4M improved dissolution rate slightly but reduced aerosolisation performances dramatically. (4) The cell viability inhibition ratio of each formulation was dose dependent, the IC50 concentrations were between 1² mg·mL^-1. All excipient did not show significant cell toxicity except in formulation C.Conclusion: The preparation and evaluation methods of ETB dry powder inhalation for pulmonary delivery are successfully established; the DPI are formulated to enable efficient delivery ETB to the simulated lung in vitro; the excipient used in each formulations improve dissolution properties of DPI while show no significant cytotoxicity in vitro.