The Study On Preparation And Pharmacodynamics Of R-salbutamol Sulfate For Pulmonary Inhalation

As a kind of β2receptor agonist, salbutamol acts on the bronchial smooth muscleselectively, which can exert strong and rapid bronchodilatation effect. R-salbutamol is opticalisomer obtained from racemic salbutamol, with the advantages of high efficiency and lowtoxicity compared to racemic salbutamol.Pulmonary inhalation is an ideal administrationroute for the treatment of respiratory diseases.We focused the research on racemicsalbutamol、r-salbutamol inhalation solution, the quality research and pharmacodynamicsevaluation were conducted in this paper. Following is the main content of this study:(1) The formulation of racemic salbutamol sulfate inhalation solution was drawn up firstly.Then the quality research was conducted deeply according to the requirements ofChinese Pharmacopoeia on quality specification. Three batch preclinical samples wereprepared and the stability study was started, including influence factors trial、acceleration trial and long-term trial. On the basis of above results, the research ofr-salbutamol inhalation solution was also conducted following the same method, whichcan give necessary basis for the draft of r-salbutamol inhalation solution qualityspecification.(2) Refer to the specifications of EP7.3and USP on the inhalation formulations evaluation,particle size distribution and dose delivered uniformity of self-made preparations andcommercial products were tested by using Next generation impactor and Breath simulatormodel respectively. The results were quantitated according to the method of HPLC. Thestatistics data showed that: the FPF%(fine particle fraction) were amount to72.81%and71.97%for r-sal and rac-sal inhalation solution prepared by ourself and the meansdifference was not significant compared to ventolin(71.96%) and dafengkechuang(71.78%)at the0.05level, also the MMAD(μm,mass median aerodynamic diameter), they were3.278、3.321、3.390、3.406respectively. It was comparable on dose delivered uniformitybetween self-made preparations and commercial products (ventolin、 dafenkechuang) fordelivered rate and amount. All these results from analysis in vitro supported theformulation rationality and quality reliability of self-made preparations.(3) Model of acute asthma was constructed by using histamine to stimulate airway hyperresponsiveness of guniea pig. The pharmacodynamics of r-sal solution wereobserved through aerosolized administration with low、medium and high doses. Datasshowed that: Guniea pigs were injected intravenously hiatamine15ug/ml,0.5ml afterinhaled solution of low、medium and high doses, the rate of rise in the resistance of lungwere102.67%、55.23%、25.53%, revealing a significant difference compared with thecontrol group (425.37%) at the0.01level, and the changing rate in the compliance ofdyanamic lung increased to-62.24%、-48.82%and-25.18%compared to-83.85%ofcontrol group. There was no significant difference on the improvement of pulmonaryfunction when compared to the effect of doubled dose of rac-salbutamol, which greatlysupport the rationality and important significance for the research and development ofr-sal inhalation solution...