Studies On Powder Aerosols For Inhalation Of Fhcin

Object: It is an important attempt to develop a powder aerosolos for inhalationformulation for inhalation of FHCin, a newly discovered antiinflammatorily activecompound, isolated from Chinese herb named Kuan Ye Fan Hun Cao, the formation ofnanoparticles by chitosan and sodium tripolyphosphate cross linking, then spray-driedinto a powder aerosolos for inhalation to inhalation for the treatment of acute lunginjury, pulmonary edema.Method: Firstly, HPLC method was established to determine the content and invitro release of FHCin. And made a quality evaluation system including the chemicalproperties of powder aerosolos for inhalation and inhaled performance evaluation. Then,Multi-index evaluation was performed to optimize the preparation process of FHCinpowder aerosolos for inhalation. Yield, the angle of repose, aerodynamic particle sizeand moisture content were the evaluation index. Thirdly, HPLC method was establishedto determine the content of FHCin in rat plasma. Compare with FHCin solutiontransjugular by injection, the FHCin has been determined via the lung inhalation bypowder aerosolos for inhalation. Finally, to study the biocompability of FHCin powderaerosolos for inhalation, we can make sure whether the powder aerosolos for inhalationformulations fits for pulmonary inhalation.Result: The extreme optimization of the spray drying variables was: atomizingpressure200kPa; air flow0.5m3/min; feed flow rate7.0mL/min and inlet temperature110℃. Nanoparticles preparation process as well as the prescription of screening visitsand the final choice of the reaction at room temperature, the time of15min,300W,3min ultrasound obtained nanoparticles, chitosan concentration of2mg/mL, sodiumtripolyphosphate as1mg/mL, the volume of both the ratio of2:1;5%mannitol;2%poloxamer188, and the proper amount of L-leucine. The powder aerosolos forinhalation has these properties inculding the uniform size of distribution, highlywrinkled characterized irregular particles, good dispersibility and without aggregation phenomenon; encapsulation efficiency was22%of the goods; the yield was62.6%;moisture content was2.07%; repose angle was36.09°; aerodynamic particle size was4.16μm; emptying rate was95.85%; DSC display the FHCin as amorphous in powderaerosolos for inhalation. Two different routes of administration rats were given the samedose of FHCin powder aerosolos for inhalation and FHCin solution, which showedpharmacokinetic parameters were significantly different. We found the twoadministrations were one-compartment model. Cell morphology observation and MTTdetection both results show that: experiments obtained powder aerosolos for inhalationare qualified in1.250,0.625,0.312,0.156,0.078and0.039mg/mL. Hemolysisexperiments on a comprehensive visual observation and spectrophotometry, powderaerosolos for inhalation can cause hemolysis, and hemolytic rate was more than5at aconcentration of1%, which does not meet the biomedical materials hemolytic rateassessment standards.Conclusions: The external standard method has good accuracy, precision andrecovery without a suitable internal standard in the measured chromatographicconditions, which was the basic of the standards and providing judgment on thescreening process. Preparation of chitosan nanoparticles and powder for inhalationprocess is mature and stable, prescription investigated using single factor. HPLCmethod, the homemade rat lung inhalation model is simple, in the lung inhalation routeof administration, more advanced and successful way. The pharmacokinetic resultssuggest that the preparation of our lungs selective.