To Study The Effect Of In Vitro Factors On The Particle Size And Distribution Of PMDI Tested By NGI And The Aerodynamic Particle Size Distribution Of Albuterol Sulfate Quantitative Inhalation Aerosol

Objectives(1)The aerodynamic particle size of metered-dose aerosol is a key parameter that needs to be strictly controlled.It determines the deposition position of particles in the respiratory tract and is closely related to the efficacy of the drug administered.The impactor NGI will be affected by various factors in the environment when testing the particle size of the inhaled formulation.This study explored the impact of ambient temperature,humidity,test flow rate and electrostatic effects on NGI test results.(2)Salbutamol sulfate inhalation aerosol is a commonly used antiasthmatic drug,which can quickly relieve bronchospasm during acute asthma attacks.In recent years,as the incidence of asthma and COPD has increased year by year,the clinical dosage of albuterol sulfate aerosol has increased significantly.However,due to the difficulty of aerosol technology and the difficulty of research and development,there are fewer domestic production and research enterprises Therefore,the demand for imported drugs for clinical use is large.Therefore,the consistency evaluation method of aerosol is of great significance,and the aerodynamic particle size is an important item for in vitro evaluation.Pharmaceutical consistency evaluation,as well as ideas for new drug development.Methods:(1)Select a commercially available typical quantitative inhalation aerosol,use NGI to measure the aerodynamic particle size of the aerosol under different conditions,and calculate the aerodynamic parameters through the relevant software: fine particle fraction(FPF),aerodynamic mass Medium diameter(MMAD),geometric standard deviation(GSD),and drug deposition curves were established.(2)NGI was used to test the aerodynamic particle size of the salbutamol sulfate aerosols of the two factories,to establish the drug deposition curve,analyze the aerodynamic parameters,and establish a mathematical model to compare the particle size of the two albuterol sulfate aerosols.Results:(1)This study explored the effects of ambient temperature,humidity,flow rate,and electrostatic effects on NGI test quantitative inhalation aerosols: it was found that ambient temperature,humidity,flow rate can significantly affect the size and distribution of particle size,and electrostatic effects affect the NGI The total mass of the drug,but does not affect the size of the drug particles,that is,only affects the distribution of particles.The main performance is as follows: compared with room temperature conditions,the mass of particles entering the impactor stage under low temperature test conditions is significantly reduced,and the particle size shifts to a lower order,so the temperature not only affects the particle size but also Distribution;compared with high humidity conditions,under low humidity test conditions,the mass of particles entering the impactor stage did not change significantly,and the particle size entering the impactor shifted to a lower order,so humidity does not affect the artificial throat stage The particle deposition of only affects the size and distribution of the particle size of the impactor stage;under the test conditions of different flow rates,with the increase of the flow rate,the significance of artificial throat deposition decreases,and the impact of the impactor stage increases The particle size distribution entering the impactor has also changed.As the flow rate increases,the particle size shifts to higher stages,so the flow rate affects not only the particle size but also the particle size distribution.In contrast,the amount of drug deposited in the impactor stage of the static control group is higher,the NGI curve does not shift,and the electrostatic effect affects the total mass of the drug entering the NGI,but does not affect the size of microparticles.(2)There is a certain difference in the size and distribution of the fine particles of two kinds of albuterol sulfate quantitative inhalation aerosol.The FPF of the aerosol sample of factory B is larger than that of factory A,and the GSD and MMAD are smaller than that of factory A.The size and distribution of the fine particle size of factory A are low;According to the model equations,the particle size distribution of the aerosol fine particles in Factory B is relatively regular.Conclusion:(1)When using NGI to test the particle size of metered-dose inhalation aerosol,the relevant environmental conditions should be stipulated.It is recommended that the ambient temperature be uniformly regulated,that is,after pre-cooling at 5 ℃ for 90 minutes,it is recommended to uniformly regulate the environmental humidity,That is,the measurement under high humidity,it is recommended to uniformly regulate the flow rate,that is,the measurement under the condition of 30 L / min,according to the conditions of the laboratory,the relevant equipment should be used to avoid the effect of static electricity as much as possible.(2)There are certain differences in the size and distribution of the fine particle size of the two kinds of albuterol sulfate quantitative inhalation aerosols.The mathematical model fitted by the particle size and drug deposition amount is an effective means to study the particle size prediction.