ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-1

年代:1999

数据来源: MAL

摘要:

ABSTRACTPast success of topical delivery to the lung stems more from the therapeutic nature of drugs used rather than the delivery device. Both the pressurized metered dose inhaler (pMDI) and the dry powder inhaler (DPI) are inefficient, placing a small fraction of the dose at the site of action. Most of the drug deposits in the mouth and is swallowed. Modifications to the pMDI may redress this by improving the coordination of dose generation and inspiration, or by the use of spacers. The DPI can be improved by the use of special excipients. Nevertheless, fundamental weaknesses that limit improvements in targeting drugs to the lung remain. Ideally, a stationary or slow-moving cloud of a selected particle size distribution should be generated at the source by the device. The rate of cloud generation should be such that a patient can accommodate it during a slow inspiration. Many new devices are in development, harnessing one or more of these principles. Respimat (Boehringer Ingelheim, Ingelheim am Rhein, Germany), a soft mist inhaler, shows particular promise. It generates a fine slow-moving cloud over a period exceeding 1 second and incorporates many design features to win patient acceptance.

ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-3

年代:1999

数据来源: MAL

摘要:

ABSTRACTInterest in the use of solution inhalers and dry powder inhalers (DPIs) has increased in recent years, broadening from systems for the delivery of traditional respiratory medications to the delivery of inhaled proteins, peptides, and analgesics. This has led to numerous developments and a range of inhaler designs and technology, each with advantages and distinctive features. Novel devices for aerosolization of solutions can be broadly divided into three main classes: adaptive aerosol delivery devices, metered dose liquid inhalers (MDLIs), and breath-actuated nebulizers. Similarly, the wide range of DPIs in development can be classified generally according to their means of storing and providing the drug, that is, as single capsules, a bulk reservoir, or multiunit-dose devices. Choice of a system for delivering a liquid solution is based on a number of factors (e.g., ease of use, convenience, aerosol properties, dose delivery, and drug deposition), the combination of which will have an impact on the single most important factor: clinical benefit. Ultimately, the patient must be able to use the device easily, maintain it, and derive clinical benefit from the drug delivered by the system. Physicians and patients must recognize that if one system does not work, an alternative must be tried.

ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-9

年代:1999

数据来源: MAL

摘要:

ABSTRACTAerosolization of a drug solution in a handheld device for inhalation therapy can be achieved either by vibration or extrusion through a fine nozzle. The latter method does not necessitate the use of an electrical power source and has been developed further in Respimat. The device was adapted for mass production, selecting appropriate materials for the desired size and weight as well as for stability and technical performance. After optimization of the nozzle design, Respimat produced encouraging results in its first lung deposition study in volunteers compared with a chlorofluorocarbon-driven metered dose inhaler (CFC-MDI). Respimat is a reusable device with a mode of action that differs from those of other inhalers. The mechanical power from a coiled spring forces a metered volume of drug solution through a nozzle in a unique component, the uniblock. The convergence of two fine jets of liquid generates a slow-moving aerosol of soft mist. The fine particle fraction in the aerosol, determined from experiments with the Anderson Cascade Impactor (Anderson Instruments, Inc., Smyrna, GA), is approximately 66% for an aqueous drug solution and 81% for an ethanolic solution. This value is about 2.5 times higher than the fine particle fractions determined for CFC-MDIs, and the velocity is about five times lower (e.g., 10 m/s for an aqueous solution), with both factors contributing to the improved lung deposition. In addition, the dose release duration from Respimat is considerably longer than that from CFC-MDIs at approximately 1.2 seconds, allowing more time for the patient to coordinate actuation and inspiration. The reliability and consistency of dose delivery from Respimat also have been confirmed.

ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-19

年代:1999

数据来源: MAL

摘要:

ABSTRACTMany new inhaler devices and formulations involving pressurized metered dose inhaler (pMDI), dry powder inhaler (DPI), and liquid spray technologies are currently being developed. Some of these novel drug delivery products deposit a greater percentage of the drug dose in the lungs than a conventional chlorofluorocarbon (CFC)-based pressurized aerosol, hence providing better drug targeting to the required site of drug action. The noninvasive imaging technique of gamma scintigraphy provides an accurate quantification of the amount of drug deposited in the lungs from inhaler devices together with an assessment of deposition in different lung regions. Respimat (Boehringer Ingelheim, Ingelheim am Rhein, Germany) is a novel liquid spray "soft mist inhaler" that more than doubles deposition in the lungs compared with a pMDI and reduces oropharyngeal deposition, thus providing a degree of drug targeting comparable to that from a spacer device. These data suggest that Respimat should be a valuable addition to the range of devices available for inhalation therapy.

ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-25

年代:1999

数据来源: MAL

摘要:

ABSTRACTInhalation is regarded as the most effective treatment for respiratory disorders. Boehringer Ingelheim (Ingelheim am Rhein, Germany) has developed Respimat, a soft mist inhaler that delivers a metered dose of drug solution as an aerosol with a high "fine particle fraction" approximately five times slower than aerosols from chlorofluorocarbon-driven metered dose inhalers (CFC-MDIs). These characteristics have led to improved drug deposition in the lungs. In scintigraphic studies using fenoterol and flunisolide, mean drug delivery to the lungs was 31.1 to 44.6% of the dose delivered using Respimat compared with less than 20% using a CFCMDI. Clinical studies in asthmatic patients using inhaled fenoterol alone (Berotec; Boehringer Ingelheim) or combined with ipratropium bromide (Berodual; Boehringer Ingelheim) confirmed the hypothesis that lower doses administered using Respimat should produce bronchodilator effects similar to those obtained with standard doses administered via a CFC-MDI. For Berotec, 12.5 or 25 μadministered by Respimat was therapeutically equivalent to either 100 or 200 μg administered by a CFC-MDI. For Berodual, bronchodilatory effects of 25/10- or 50/20-μg doses using Respimat tended to be close or slightly superior to those of 100/40 μg using a CFC-MDI. Safety profiles did not differ between Respimat and CFC-MDI administration in either trial. Patients with airway hyperreactivity who inhaled placebo or drug solutions containing different preservatives and stabilizers had low incidences of paradoxical bronchoconstriction or asymptomatic decreases in lung function, which were similar with Respimat and a CFC-MDI. Furthermore, facial deposition data suggest a low risk of untoward effects even in potential misuse situations. Thus, Respimat promises to be a valuable alternative to conventional CFC-MDIs, with the additional benefit of improved drug targeting to the lu

ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-33

年代:1999

数据来源: MAL

ISSN:0894-2684    

DOI:10.1089/jam.1999.12.Suppl_1.S-41

年代:1999

数据来源: MAL