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

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          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 (2) Methods: Portions of admixtures were withdrawn at certain time intervals after mixing and were tested by pH determination, osmolarity measurement, and high-performance liquid chromatography (HPLC) assay of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.

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          Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size.

          Peter Barnes, Shariq Usmani, Martyn Biddiscombe … (2005)
          Aerosol particle size influences the extent, distribution, and site of inhaled drug deposition within the airways. We hypothesized that targeting albuterol to regional airways by altering aerosol particle size could optimize inhaled bronchodilator delivery. In a randomized, double-blind, placebo-controlled study, 12 subjects with asthma (FEV1, 76.8 +/- 11.4% predicted) inhaled technetium-99m-labeled monodisperse albuterol aerosols (30-microg dose) of 1.5-, 3-, and 6-microm mass median aerodynamic diameter, at slow (30-60 L/min) and fast (> 60 L/min) inspiratory flows. Lung and extrathoracic radioaerosol deposition were quantified using planar gamma-scintigraphy. Pulmonary function and tolerability measurements were simultaneously assessed. Clinical efficacy was also compared with unlabeled monodisperse albuterol (15-microg dose) and 200 microg metered-dose inhaler (MDI) albuterol. Smaller particles achieved greater total lung deposition (1.5 microm [56%], 3 microm [50%], and 6 microm [46%]), farther distal airways penetration (0.79, 0.60, and 0.36, respective penetration index), and more peripheral lung deposition (25, 17, and 10%, respectively). However, larger particles (30-microg dose) were more efficacious and achieved greater bronchodilation than 200 microg MDI albuterol (deltaFEV1 [ml]: 6 microm [551], 3 microm [457], 1.5 microm [347], MDI [494]). Small particles were exhaled more (1.5 microm [22%], 3 microm [8%], 6 microm [2%]), whereas greater oropharyngeal deposition occurred with large particles (15, 31, and 43%, respectively). Faster inspiratory flows decreased total lung deposition and increased oropharyngeal deposition for the larger particles, with less bronchodilation. A shift in aerosol distribution to the proximal airways was observed for all particles. Regional targeting of inhaled beta2-agonist to the proximal airways is more important than distal alveolar deposition for bronchodilation. Altering intrapulmonary deposition through aerosol particle size can appreciably enhance inhaled drug therapy and may have implications for developing future inhaled treatments.
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            Mechanisms of Pharmaceutical Aerosol Deposition in the Respiratory Tract

            Yung Sung Cheng (2014)
            Aerosol delivery is noninvasive and is effective in much lower doses than required for oral administration. Currently, there are several types of therapeutic aerosol delivery systems, including the pressurized metered-dose inhaler, the dry powder inhaler, the medical nebulizer, the solution mist inhaler, and the nasal sprays. Both oral and nasal inhalation routes are used for the delivery of therapeutic aerosols. Following inhalation therapy, only a fraction of the dose reaches the expected target area. Knowledge of the amount of drug actually deposited is essential in designing the delivery system or devices to optimize the delivery efficiency to the targeted region of the respiratory tract. Aerosol deposition mechanisms in the human respiratory tract have been well studied. Prediction of pharmaceutical aerosol deposition using established lung deposition models has limited success primarily because they underestimated oropharyngeal deposition. Recent studies of oropharyngeal deposition of several drug delivery systems identify other factors associated with the delivery system that dominates the transport and deposition of the oropharyngeal region. Computational fluid dynamic simulation of the aerosol transport and deposition in the respiratory tract has provided important insight into these processes. Investigation of nasal spray deposition mechanisms is also discussed.
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              Nebulizers for drug delivery to the lungs.

              Warren H Finlay, Andrew Martin (2015)
              Nebulizers are the oldest modern method of delivering aerosols to the lungs for the purpose of respiratory drug delivery. While use of nebulizers remains widespread in the hospital and home setting, certain newer nebulization technologies have enabled more portable use. Varied fundamental processes of droplet formation and breakup are used in modern nebulizers, and these processes impact device performance and suitability for nebulization of various formulations.
              Article 0 comments Cited 31 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceutics
                Journal ID (iso-abbrev): Pharmaceutics
                Journal ID (publisher-id): pharmaceutics
                Title: Pharmaceutics
                Publisher: MDPI
                ISSN (Electronic): 1999-4923
                Publication date (Electronic): 15 August 2020
                Publication date Collection: August 2020
                Volume: 12
                Issue: 8
                Electronic Location Identifier: 776
                Affiliations
                [1 ]Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 201203, China; 18211030015@ 123456fudan.edu.cn (Y.C.); 16301030052@ 123456fudan.edu.cn (Z.Z.); 18111030032@ 123456fudan.edu.cn (W.H.); 19211030026@ 123456fudan.edu.cn (E.L.); 19111030038@ 123456fudan.edu.cn (R.W.)
                [2 ]Department of Emergency Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; du.shilin@ 123456zs-hospital.sh.cn
                [3 ]The Institutes of Integrative Medicine of Fudan University, Shanghai 200040, China
                [4 ]Shanghai Mental Health Center, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, China
                Author notes
                [* ]Correspondence: shaxy@ 123456fudan.edu.cn (X.S.); mayan@ 123456smhc.org.cn (Y.M.); Tel.: +86-21-51980072 (X.S.)
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: pharmaceutics-12-00776
                DOI: 10.3390/pharmaceutics12080776
                PMC ID: 7466038
                PubMed ID: 32824123
                SO-VID: f9f8d361-61ac-4c3b-b9a3-ee7233c99fde
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 02 July 2020
                Date accepted : 11 August 2020
                Categories
                Subject: Article

                Keywords: atrovent®,ventolin®,bricanyl®,pulmicort®,fluimucil®,ipratropium,nebulization,compatibility,aerosol characteristics,simultaneous inhalation
                Data availability:
                Keywords: atrovent®, ventolin®, bricanyl®, pulmicort®, fluimucil®, ipratropium, nebulization, compatibility, aerosol characteristics, simultaneous inhalation

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