Q I was asked to compound albuterol with cromolyn sodium in an inhalation solution. Should I use citric acid?
A Albuterol and cromolyn sodium are compounded for nebulization, to provide a rapid response by distributing a concentrated dose into the bronchioles. Nebulized solutions inhalation may be oral or intranasal to achieve local or systemic effect. The fine droplets (0.5 to 10 microns, preferably ~3 to 6 microns) of the solution are delivered to the bronchioles from a face mask connected to the nebulizer, or by using a tent or an intermittent positive pressure breathing mechanism. Besides droplet size, other considerations are the vehicle, pH/need for buffers, tonicity of the solution, need for preservatives, solution viscosity, and surfactant requirements. These factors all impact the absorption of the medications. For this question, tonicity and pH are important. The solution tonicity should be isotonic, about the same as "normal saline," 0.9% sodium chloride (~290 mOsm); enhanced absorption of the medication is achieved when the solution is slightly hypotonic. Tonicity adjustments may be needed for a particular formulation when changing active ingredients or varying concentrations per patient's requirements. Most often, the adjustment can be achieved with sodium chloride. Occasionally, calculation of a particular formulation's tonicity reveals isotonicity or hypotonicity, obviating the need for adjustment. Buffering the solution to neutral (~pH 7, body fluid pH) is important. At acidic pH, the cough reflex can be induced and the medication expelled.Weaker buffers (eg, citric acid) will help provide pH 7 and avoid potential pulmonary pH effects that can aid growth of microbes. The following informational formulations help illustrate these points:
1. Cromolyn Sodium Solution for Inhalation 1%, Preservative- Free:
Dissolve 1 g cromolyn sodium in sufficient sterile water for inhalation to make 100 mL.
2. Albuterol Inhalation Solution 0.5%, Preservative-Free
Albuterol Sulfate USP: 0.5 g
Citric Acid, Anhydrous USP: 0.1 g
Sodium Chloride USP: 0.8 g
Sterile Water for Inhalation USP qs ad 100 mL
No claims are made as to the uses, safety, efficacy, or bioavailability of these products. Reference available on request.
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Mr. Erickson is director of professional affairs at Gallipot Inc.