目的 通过考察溶液型和混悬型吸入气雾剂在不同条件下的递送剂量和空气动力学粒径分布,研究环境温度、环境湿度以及样品罐体温度对药物制剂特性的影响,为确定制剂配方、确定药品说明书和指导临床用药提供依据。方法 分别在环境温度(18 ℃、22~25 ℃、32 ℃)、环境湿度、样品罐体温度(5 ℃、22~25 ℃、40 ℃)的条件下,采用DUSA管法及新一代级联撞击器(new generation impactor,NGI)测试溶液型异丙托溴铵吸入气雾剂(ipratropium bromide,IPT)和混悬型布地奈德(budesonide,BUD)的递送剂量及空气动力学粒径分布。结果 环境温度、环境湿度、样品罐体温度对2种类型的吸入气雾剂(metered dose inhaler,MDI)的递送剂量均无明显影响。环境温度对其微细粒子分数(fine particle fraction,FPF)无明显影响,其结果差异不具有统计学意义(P＞0.05);但环境湿度及样品罐体温度有显著影响,与低(30%)及中(50%)环境湿度相比,高环境湿度(80%)条件下得到的FPF分别减少了17.94%和13.69%(BUD)、12.74%和9.03%(IPT)(P＜0.05),RH 30%与RH 50%结果均无显著差异;与样品罐体常温(22~25 ℃)及高温(40 ℃)相比,样品罐体温度在低温(5 ℃)下测得的 FPF分别减小了22.80%和21.86%(BUD)、26.55%和26.85%(IPT),结果具有极显著差异(P＜0.01);样品罐体常温与高温间均无显著差异。结论 在进行吸入气雾剂制剂特性检查时,应尽可能控制环境的温湿度(22~25 ℃、RH 50%)和样品罐体温度(室温22~25 ℃),也提示低温贮存的MDI在使用前应恢复至室温。
Abstract
OBJECTIVE To investigate the effects of ambient temperature,humidity and canister temperature on the inhalation drug delivery systems by examining the delivery dose and the aerodynamic particle size distribution. Two common inhalation drug delivery systems were choosenunder different conditions,the solution and the suspension type inhalation aerosol, in order to determine the formulationof the preparation and drug description, and provide the basis for guiding the clinical medication. METHODS The DUSA tube method and new generation impactor (NGI) was used to determine the delivery dose and aerodynamic particle size distribution of ipratropium bromide(IPT) and budesonide(BUD) inhaled aerosol at different ambient temperature(18 ℃, 22-25 ℃, 32 ℃), ambient humidity, and canister temperature(5 ℃, 22-25 ℃,40 ℃)respectively. RESULTS The ambient temperature, ambient humidity and canister temperature had no significant effect on the delivery dose of the two types of MDI. The ambient temperature had no significant effect on the fine particle fraction (FPF) of the two aerosol agents, and the difference of FPF under different ambient temperature was not statistically significant (P>0.05). Environmental humidity and drug canister temperature had significant effects on the FPF. Compared with low humidity 30% and medium humidity 50%, the FPF obtained at high ambient humidity 80% decreased 17.94% and 13.69% (BUD), 12.74% and 9.03% (IPT) (P<0.05), but there was no significant difference between RH 30% and RH 50%. Compared with room temperature (22-25 ℃) and high temperature (40 ℃), the FPF measured at low temperature (5 ℃) decreased by 22.80% and 21.86% (BUD), 26.55% and 26.85% (IPT) respectively(P<0.01), but there was no significant difference between room temperature and high temperature. CONCLUSION The temperature and humidity of the environment (22-25 ℃, RH 50%)and the sample canister temperature should be controlled as far as possible when the performance of the inhaled aerosol preparation are tested.At the same time, it is suggested that MDI stored at low temperature shall be recovered to room temperature before use.
关键词
吸入气雾剂 /
递送剂量 /
空气动力学粒径分布 /
新一代级联撞击器 /
环境因素 /
吸入有效性
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Key words
aerosol inhalation /
delivery dose /
aerodynamic particle size distribution /
new generation cascade impactor /
environmental factor /
inhalation effectiveness
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中图分类号：
R944
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参考文献
[1] XUE F, JIN F. Role of inhalations in asthma and chronic obstructive pulmonary disease treatment. World Clin Drugs, 2012, 33(4): 245-249.
[2] AGU R U,UGWOKE M I,ARMAND M, et al. The lung asa route for systemic delivery of therapeutic proteins and peptides. Respir Res, 2001, 2(4): 198-209.
[3] SUAREZ S, HICKEY A J. Drug properties affecting aerosol behavior. Respir Care, 2000, 45(6):652-666.
[4] WEI N Y, ZHOU Y, CHEN C C, et al. Comparison of measurement methods of delivered-dose uniformity of salbutamol sulfate inhalation aerosol. Chin J New Drugs(中国新药杂志), 2018, 27(4):405-408.
[5] XU Y W, LIANG C R, XIE Y C, et al. Comparison of two methods for determination of budesonide aerosol droplet distribution. Chin J Pharm(中国医药工业杂志), 2013, 44(9):921-924.
[6] CLARK A R. Metered atomisation for respiratory drug delivery. Loughborough: Loughborough University Technol, 1991.
[7] WILSON A F, MUKAI D S, AHDOUT J. Effect of canister temperature on performance of metered-dose inhalers. Am Rev Respir Dis, 1991, 143(5 Pt 1):1034-1037.
[8] MORIN C M D, IVEY J W, TITOSKY J T F, et al. Performance of pressurized metered-dose inhalers at extreme temperature conditions. J Pharm Sci, 2014, 103(11):3553-3559.
[9] SHEMIRANI F M, HOE S, LEWIS D, et al. In vitro investigation of the effect of ambient humidity on regional delivered dose with solution and suspension MDIs. J Aerosol Med Plum D, 2013, 26 (4):215-222.
[10] STEIN S W, MYRDAL P B. The relative influence ofatomization and evaporation on metered dose inhaler drug delivery efficiency. Aerosol Sci Technol, 2006, 40(5):335-347.
[11] LANGE C F, FINLAY W H. Overcoming the adverse effect of humidity in aerosol delivery via pressurized metered-dose inhalers during mechanical ventilation. AM J Resp Crit Care, 2000, 161(5):1614-1618.
[12] SONG X, HU J, ZHAN S, et al. Effects of temperature and humidity on laser diffraction measurements to jet nebulizer and comparison with NGI. AAPS Pharm Sci Tech, 2016, 17(2):380-388.
[13] ELNA B, JAN O S, LARS A. Determination of nebulizer droplet size distribution: amethodbased on impactor refrigeration. J Aerosol Med, 2007, 20(2):97-104.
[14] ABDELRAHIM M E. Aerodynamic characteristics of nebulized terbutaline sulphateusing the andersen cascade impactor compared to the next generation impactor. Pharm Dev Technol, 2011, 16 (2):137-145.
[15] MARTIN A R, FINLAY W H. The effect of humidity on the size of particles delivered from metered-dose inhalers. Aerosol Sci Tech, 2005, 39(4):283-289.
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脚注
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基金
国家重大新药创制科技专项资助(2017ZX09201002-002);中国药用吸入气雾剂CFCs淘汰行业计划资助(MDI-LC-11);国家药典委员会药品标准制修订研究课题资助(2019Y13)
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