Respimat

S. P. Newman, J. Brown, K. P. Steed, S. J. Reader, and H. Kladders, Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines Comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices, Chest 113 951 (1998). 

The Respimat inhaler was recently launched in Germany as a combination product of fenoterol and ipratropium hydrobromide (Berodual) and was licensed for the treatment of chronic obstructive airway disease. A large body of literature now exists documenting the aerosol characteristics and clinical performance of the Respimat inhaler with a number of different drugs [274,275]. Aerosolized formulations include the steroids budesonide and flunisolide in addition to the p agonist fenoterol as well as the commercially available combination product of fenoterol and ipratropium bromide [276-281],... 

Aerosols generated from the Respimat inhaler have been characterized as having a prolonged aerosol cloud duration compared to MDIs and have a slower cloud velocity as measured using video camera imaging. Hochrainer et al. (2005) measured the cloud duration of the Respimat aerosol to be 0.2-1,6 s compared to less than 0.2 s for HFA and CFC MDIs. Aerosol velocities have been reported as less than lm/s for the Respimat, compared to 6-8m/s for CFC MDI inhalers [283], While a degree of patient coordination is required to actuate the Respimat and to inhale,... 

FIGURE 6 Respimat Inhaler. (Courtesy of Boehringer Ingelheim.)... 

Aqueous and ethanolic formulations have been employed with the Respimat and the in vitro aerosol performance determined. Zierenberg (1999) reported fine-particle fractions of 66% for an aqueous fenoterol formulation and 81% for an ethanolic flunisolide formulation. The respective MMADs were 2.0 0.4 pm for the aqueous formulation and 1.0 0.3 pm for the ethanolic formulation [284],... 

Patel, K. R., Pavia, D., Lowe, L., and Spiteri, M. (2006), Inhaled ethanolic and aqueous solutions via respimat soft mist inhaler are well-tolerated in asthma patients, Respiration, 73,434 140. 

Voshaar, T., Hausen, T., Kardos, P, et al. (2005), Inhalation therapy with respimat soft inhaler in patients with COPD and asthma, Pneumologie, 59,25-32. 

Kassner, F., Hodder, R., and Bateman, E. D. (2004), A review of ipratropium bromide/fenoterol hydrobromide (berodual) delivered via respimat soft mist inhaler in patients with asthma and chronic obstructive pulmonary disease, Drugs, 64, 1671-1682. 

Pitcairn, G, Reader, S., Pavia, D., and Newman, S. (2005), Deposition of corticosteroid aerosol in the human lung by respimat soft mist inhaler compared to deposition by metered dose inhaler or by turbuhaler dry powder inhaler, J. Aerosol Med., 18, 264-272. 

Vincken, W., Dewberry, H., and Moonen, D. (2003), Fenoterol delivery by respimat soft mist inhaler versus CFC metered dose inhaler Cumulative dose-response study in asthma patients, J. Asthma, 40, 721-730. 

Schumann, W., Schmidtmann, S., Moroni, P., Massey, D., and Qidan, M. (2005), Respimat soft mist inhaler versus hydrofluoroalkane metered dose inhaler Patient preference and satisfaction, Treat. Respir. Med.., A, 53-61. 

Pavia, D., and Moonen, D. (1999), Preliminary data from phase II studies with respimat, a propellant-free soft mist inhaler, J. Aerosol Med., 12(Suppl. 1), S33-39. 

Hochrainer, D., Holz, H., Kreher, C., Scaffidi, L., Spallek, M., and Wachtel, H. (2005), Comparison of the aerosol velocity and spray duration of respimat soft mist inhaler and pressurized metered dose inhalers, /. Aerosol Med., 18,273-282. 

Newman examined the deposition profiles in patients of several developmental Respimat prototypes using gamma scintigraphic techniques. In these studies, the deposition of the bronchodilator fenoterol and the corticosteroid flunisolide were examined. Fenoterol in the Respimat was formulated in an aqueous medium, and flunisolide was formulated in 96% ethanol. The experimental data from these studies are shown in Table 12. 

The performance of the Respimat was clearly improved for the flnal prototype compared with Prototype III. Drug deposition in the lungs increased from approximately 31% to 39% for the fenoterol, and from about 40% to 45% for the drug compound of flunisolide respectively. At the same time, the oral-pharyngeal deposition decreased from approximately 54% to 37%... 

Table 12 Average deposition data using the Respimat (% of the emitted dose)...

Respimat is considerably longer than that from CFC MDIs at approximately... 

In scintigraphic studies using fenoterol and flunisolide, mean drug delivery to the lungs was 31-45% of the dose delivered using Respimat compared with less than 20% using a CFC MDI. Safety profiles did not differ between Respimat and CFC MDI administration. Facial deposition data suggested a low risk of untoward effects even in potential misuse situations for Respimat. 

Lung deposition of fenoterol with the use of Respimat, a MDI, and a MDI plus Aerochamber in healthy volunteers was found to be 39, 11 and 10%, respectively. The use of Respimat resulted in uniform deposition of drugs throughout the peripheral, intermediate, and central lung zones. On the other hand, oropharyngeal deposition of fenoterol from Respimat was lower than that from the MDI (37% vs 72%). 

In 36 patients with chronic obstructive pulmonary disease, the bron-chodilator effect of ipratropium bromide was greater with delivery via Respimat (total dose 160 ttg) than via MDI (total dose of 320 (tg). Between 45 min after the first drug inhalation and 45 min after the final dose, a greater bronchodilatory effect was obtained at half the cumulative dose of ipratropium. The safety profile was similar. 

Kunkel, G., Magnussen, H., Bergmann, K., Juergens, U. R., de Mey, C., Freund, E., Hinzmann, R., and Beckers, B. Respimat (a new soft mist inhaler) delivering fenoterol plus ipratropium bromide provides equivalent bronchodilation at half the cumulative dose compared with a conventional metered dose inhaler in asthmatic patients. Respiration 67 306-314,2000. 

Steed, K. P., L. J. Towse, B. Freund, and S. P. Newman. 1997. Lung and oropharyngeal depositions of fenoterol hydrobromide delivered from the prototype III hand-held multidose Respimat nebuliser. Eur.. Pharmaceut. Sci. 5 55-61. 

New nebulizer delivery devices designed to deliver specific drug formulations that have undergone clinical trials to establish safety and efficacy as part of the regulatory process—e.g., Respimat and AERx. 

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