OBJECTIVE To evaluate the in vitro compatibility of inhaled budesonide suspension combined with inhaled ipratropium bromide solution or inhaled ambroxol hydrochloride solution or others in combination with nebulization.

METHODS A high-performance liquid chromatography combined with a breath simulator and a new generation impactor were used to study the delivery rate, total volume and aerodynamic particle size distribution of the combined nebulization, and to investigate its physicochemical compatibility.

RESULTS When inhaled budesonide suspension is used in combination with different inhaled drugs, such as ipratropium bromide, there were significant differences in the delivery rate and total drug substance delivered compared to nebulization alone. The delivery rate of budesonide was reduced in all cases, except for the combination of three drugs with ipratropium bromide, where the delivery rate was significantly reduced (>15%), but the total delivery was essentially the same. In addition, the delivery rate of ipratropium bromide decreased by 33%, the delivery rate of ambroxol increased by 25%, and the total delivery of ambroxol, terbutaline, and acetylcysteine also significantly increased, by 56%, 48% and 49%, respectively. The fine particle dose, fine particle fraction, and mass median aerodynamic diameter changes were all less than 10%. The pH value, osmotic pressure, and active ingredient content of the mixed solution were stable within 30 minutes.

CONCLUSION The evaluation protocol established in this study can more comprehensively investigate the compatibility of inhaled solutions combined with nebulization. The research results improve the compatibility data of budesonide suspension for inhalation combined with nebulization, providing data support for clinical rational use of combined nebulization medication.