Compatibility and aerosol characteristics of beclomethasone mixed with N-acetylcysteine

Abstract

Mixing different kind inhalation medications for simultaneous inhalation is widely used in the treatment of chronic respiratory diseases, and it can minimize the administration time and improve patient adherence. To our knowledge, it is unclear whether beclomethasone (BDP, Clenil®) can bemixed with acetylcysteine (NAC, Fluimucil®), because the in vitro physico-chemical compatibility and aerosol characteristics of the mixture are unknown. In this study, we investigated physical compatibility, including the appearance, pH, osmotic pressure and chemical stability, as well as aerosol characteristics, including particle size corresponding to 10%/50%/90% of the cumulative percentage of total particle volume (X10/X50/X90), volume median droplet diameter (VMD), mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD) and geometric standard deviation (GSD), delivery rate, and total delivery of the above solutions. After mixing, there were no significant changes in visual appearance, pH, osmolality and drug content of the mixtures at room temperature for 12 h. The FDP of BDP in the mixture decreased by 16.49%, whereas the NAC increased by 10.85%. The delivery rates of BDP and NAC in the mixture decreased by 66.05% and 45.54%, and total delivery increased by 13.20% and 25.29%, respectively. However, the MMAD, FPF, particle size and GSD of the mixture were almost unchanged. We demonstrated that these admixtures are physico-chemically compatible but that coadministration of beclomethasone with acetylcysteine can markedly affect output and aerosol characteristics.

Keywords: Acetylcysteine; Aerosol characteristics; Beclomethasone; Clenil®; Compatibility; Fluimucil®; Stability.

Fig. 1

Schematic diagram of NGI device assembly.

Fig. 2

HPLC chromatograms of two inhaled solutions/suspensions and their reference substance of BDP and mixtures, a. Reference substance of BDP (240 nm); b. BDP in Clenil® at 0 h (240 nm); c. BDP in Clenil® at 0.5 h (240 nm); d. BDP in Clenil® at 12 h (240 nm); e. BDP in Fluimucil®/Clenil® at 0 h (240 nm); f. BDP in Fluimucil®/Clenil® at 0.5 h (240 nm); g. BDP in Fluimucil®/Clenil® at 12 h (240 nm); h. Reference substance NAC(214 nm); i. NAC in Fluimucil® at 0 h (214 nm); j. NAC in Fluimucil® at 0.5 h (214 nm); k. NAC in Fluimucil® at 0.5 h (214 nm); l. NAC in Fluimucil®/Clenil® at 0 h (214 nm); m. NAC in Fluimucil®/Clenil® at 0.5 h (214 nm); n. NAC in Fluimucil®/Clenil® at 12 h (214 nm).

Fig. 3

Active ingredient content changes in Fluimucil®, Clenil®and Fluimucil®/Clenil®. A. change of BDP content in single drug and admixture; B. change of NAC content in single drug and admixture; Abbreviations: C®─Clenil®, F®─Fluimucil®, C®/F®─Fluimucil®/Clenil®.

Fig. 4

Amount of drug deposition on the NGI plate from single- and mixed-inhalation solutions/suspensions. A. the distribution of BDP in single dose and mixture; B. the distribution of NAC in single dose and mixture. * and ** indicate p < 0.05 and p < 0.01.

Fig. 5

Delivery rate and total delivery of two single dose inhaled solutions/suspensions and their mixtures. a. delivery rate of BDP; b. Total delivery of BDP; c. Delivery rate of NAC; d. Total delivery of NAC. * and ** indicate p < 0.05 and p < 0.01.