O'Riordan Thomas G
Pulmonary/Critical Care Division, Health Sciences Center, State University of New York at Stony Brook, Stony Brook, New York 11794-8172, USA.
Respir Care. 2002 Nov;47(11):1305-12; discussion 1312-3.
To deliver a drug by nebulization, the drug must first be dispersed in a liquid (usually aqueous) medium. After application of a dispersing force (either a jet of gas or ultrasonic waves), the drug particles are contained within the aerosol droplets, which are then inhaled. Some drugs readily dissolve in water, whereas others need a cosolvent such as ethanol or propylene glycol. Some drugs are delivered as suspensions, and the efficiency of nebulizers can be different for solutions and suspensions. Solutions are delivered more efficiently with most devices. In general, conventional ultrasonic nebulizers should not be used to aerosolize suspensions, because of low efficiency. Newer strategies to improve the delivery of non-water-soluble drugs include the use of liposomes and the milling of the drug into very small "nanoparticles." In addition to the active therapeutic ingredient and solvents, drug formulations may include buffers (the solubility of some medications is influenced by pH), stabilizers, and, in the case of multi-dose preparations, antibacterial agents. Though formulations are designed to optimize drug solubility and stability, changes in formulation can also affect inhaled mass, particle size, and treatment time, though the differences between nebulizer brands probably have a greater impact than differences in formulation. Ultrasonic and jet nebulizers may damage protein and other complex agents through heat or shear stress. Additives to multi-dose formulations, especially antimicrobial and chelating agents, may cause adverse events, so there is a trend towards single-use, preservative-free vials.
通过雾化给药时，药物必须首先分散在液体（通常为水性）介质中。在施加分散力（气体射流或超声波）后，药物颗粒包含在气溶胶液滴中，然后被吸入。一些药物易溶于水，而其他药物则需要助溶剂，如乙醇或丙二醇。一些药物以混悬液形式给药，雾化器对溶液和混悬液的效率可能不同。大多数设备对溶液的给药效率更高。一般来说，传统的超声雾化器不应用于雾化混悬液，因为效率较低。改善非水溶性药物给药的新策略包括使用脂质体以及将药物研磨成非常小的“纳米颗粒”。除了活性治疗成分和溶剂外，药物制剂可能包括缓冲剂（某些药物的溶解度受pH值影响）、稳定剂，对于多剂量制剂，还包括抗菌剂。尽管制剂旨在优化药物的溶解度和稳定性，但制剂的变化也会影响吸入量、粒径和治疗时间，不过雾化器品牌之间的差异可能比制剂差异产生的影响更大。超声雾化器和喷射雾化器可能会通过热或剪切应力破坏蛋白质和其他复杂成分。多剂量制剂中的添加剂，尤其是抗菌剂和螯合剂，可能会引起不良事件，因此有向一次性、无防腐剂小瓶发展的趋势。
