Nebulized Drug Admixtures: Effect on Aerosol Characteristics and Albuterol Output

Abstract

Although not recommended, co-administration of drugs separately prescribed for nebulization is done in real life. The impact of this practice on drug output and aerosol characteristics is poorly understood. We studied the effect of drug admixtures (DA) on aerosol characteristics and drug output of nebulized albuterol delivered by a continuous output (CONT) and a breath enhanced nebulizer (BEN). Albuterol was nebulized alone (ALB) and combined with cromolyn sodium (A+CRO), ipratropium bromide (A+IB), tobramycin (A+TOB), flunisolide (A+FLU), and n-acetylcysteine (A+NAC). A BEN (PARI LC Plus^®) and a CONT (Hudson T UP-DRAFT II^®) were tested at 8 liters per minute (Lpm) for 2 and 5 min, respectively. Albuterol output and aerosol characteristics were determined by impaction and chemical analysis. Mass median aerodynamic diameter (MMAD; µm) A+CRO reduced MMAD from 2.57 (ALB) to 1.29 with CONT. A+FLU increased MMAD from 2.71 (ALB) to 3.40 with BEN. Geometric standard deviation (GSD) A+CRO increased GSD from 2.66 (ALB) to 3.36 with CONT. GSD was 2.33 for ALB and was not changed by DA with BEN. BEN generated a smaller and less heterodisperse aerosol than CONT. Respirable fraction (RF%) was 74% for ALB and was not changed by DA with CON. A+TOB and A+FLU decreased RF% from 75%, to 70% and 67% (respectively) with BEN. Respirable mass (RM; µg) for ALB was 935 and was not changed by DA with CONT. A+IB and A+FLU increased RM from 917 (ALB) to 1172 and 1240, respectively, with BEN. Co-nebulization of albuterol with other drugs can affect its output and aerosol characteristics. In vivo data is needed to asses the clinical implications of our findings.