Inhalation solutions: which one are allowed to be mixed? Physico-chemical compatibility of drug solutions in nebulizers.

Therapy of chronic respiratory diseases often involves inhalation therapy with nebulizers. Patients often attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. This article considers the issue of physico-chemical compatibility of admixtures of drug solutions/suspensions in nebulizers. A search of databases, prescribing information and primary literature was conducted to locate literature concerning the physico-chemical compatibility of inhalation solutions/suspensions. This was supplemented by telephone interviews. Admixtures of albuterol with ipratropium and/or cromolyn, of albuterol and budesonide, or tobramycin, or colistin are physico-chemically compatible. Physico-chemical compatibility has been demonstrated for admixtures of cromolyn with albuterol and/or ipratropium and for admixtures of cromolyn and budesonide. Admixtures of budesonide with ipratropium and/or fenoterol, and admixtures of budesonide and albuterol, or cromolyn are physico-chemically compatible. Both cromolyn and colistin are incompatible with benzalkonium chloride. Admixtures should be prepared from inhalation solutions/suspensions formulated without preservatives. Besides studies of the physico-chemical compatibility, the aerodynamic behaviour of physico-chemical mixtures needs to be studied before a final recommendation of simultaneous nebulization of compatible admixtures can be made.