Compatible Stability and Aerosol Characteristics of Atrovent® (Ipratropium Bromide) Mixed with Salbutamol Sulfate, Terbutaline Sulfate, Budesonide, and Acetylcysteine.

Yiting Chen,Rui Wang,Enhao Lu,Shilin Du,Zhirui Zhang,Xianyi Sha,Wenxiu He,Yan Ma

doi:10.3390/pharmaceutics12080776

Yiting Chen, Rui Wang + Show 6 more

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https://doi.org/10.3390/pharmaceutics12080776

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Journal: Pharmaceutics	Publication Date: Aug 15, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: Fudan University, Shanghai Mental Health Center

Abstract

(1) Background: It is common practice in the treatment of respiratory diseases to mix different inhalation solutions for simultaneous inhalation. At present, a small number of studies have been published that evaluate the physicochemical compatibility and aerosol characteristics of different inhalation medications. However, none of them studied Atrovent®. Our work aims to address the lack of studies on Atrovent®. (2) Methods: Portions of admixtures were withdrawn at certain time intervals after mixing and were tested by pH determination, osmolarity measurement, and high-performance liquid chromatography (HPLC) assay of each active ingredient as measures of physicochemical compatibility. The geometrical and aerosol particle size distribution, active drug delivery rate, and total active drug delivered were measured to characterize aerosol behaviors. (3) Results: During the testing time, no significant variation was found in the pH value, the osmotic pressure, or the active components of admixtures. With the increase in nebulization volume after mixing, fine particle dose (FPD) and total active drug delivered showed statistically significant improvements, while the active drug delivery rate decreased compared to the single-drug preparations. (4) Conclusions: These results endorse the physicochemical compatibility of Atrovent® over 1 h when mixed with other inhalation medications. Considering aerosol characteristics, simultaneous inhalation is more efficient.

Highlights

Aerosol therapy is defined as an inhalation treatment that utilizes inhaler devices to transform pharmaceutical agents into aerosol form [1]
With the increase in nebulization volume after mixing, fine particle dose (FPD) and total active drug delivered showed statistically significant improvements, while the active drug delivery rate decreased compared to the single-drug preparations
The contents of active components in test samples remained basically stable within the accepted range of high-performance liquid chromatography (HPLC) error compared with those at the initial time after mixing (T0), with the exception that the content of NAC in Atrovent®/ Pulmicort® showed a slight decrease after 0.5 h (Figure 2)

Summary

Introduction

Aerosol therapy is defined as an inhalation treatment that utilizes inhaler devices to transform pharmaceutical agents into aerosol form [1]. Aerosol therapy is widely used in the diagnosis and treatment of lung pathology, including, but not limited to, chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis (CF) [2]. Used inhaler devices are classified into three types: pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), and nebulizers. Several classes of respiratory therapeutic medications, including short-acting beta receptor agonists (SABA, e.g., salbutamol sulfate), long-acting beta receptor agonists (LABA, e.g., formoterol fumarate), short-acting muscarinic antagonists (SAMA, e.g., ipratropium bromide), long-acting muscarinic antagonists (LAMA, e.g., tiotropium bromide), and inhaled corticosteroids (ICS, e.g., budesonide), have been formulated into inhalation solutions as mainstream medicines for COPD and asthma [3]

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Conclusion