Effect of extension devices on the drug deposition from inhalation aerosols

Vidgrén, M.; Paronen, T.P.; Kärkkäinen, Anna‐Mari; Karjalainen, Panu

doi:10.1016/0378-5173(87)90204-3

Cited by 39 publications

(14 citation statements)

References 10 publications

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“…In the last several years, studies have been reported that assessed the augmentation of spacer devices for the delivery of drugs to the respiratory tract using pMDIs (8)(9)(10)(11)(12)(15)(16)(17). However, comparative in vitro investigations of commercially available spacer devices are lacking.…”

Section: Spacer Devices For Pressurized Metered Dose Inhalers 403mentioning

confidence: 98%

Investigation of Some Commercially Available Spacer Devices for the Delivery of Glucocorticoid Steroids from a pMDI

Williams¹,

Patel²,

Barron

et al. 2001

Drug Development and Industrial Pharmacy

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Five commercially available spacers were investigated to determine their influence on the percentage of drug retained in the spacer device, percentage fine particle fraction (FPF), percentage deposited in the induction port, mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). Betamethasone valerate (BMV) and triamcinolone acetonide (TAA) were used as model drugs in the pressurized metered dose inhaler (pMDI) formulations containing the propellant HFA 134a. The BMV was dissolved in an ethanol/HFA 134a system, and the TAA was suspended in HFA 134a using ethanol as a dispersing agent. The metering chamber volume of the valve was either 50 microl or 150 microl. The spacer devices investigated included the ACE, Aerochamber, Azmacort, Easivent, and Ellipse spacers. Each spacer device was attached to an Andersen Cascade Impactor powered by a vacuum pump. Cascade impaction data were used to derive the percentage drug deposited in the induction port, MMAD, GSD, and FPF. The BMV particles emitted from the spacers were finer than the TAA particles because the dissolved drug precipitated as the cosolvent evaporated. The TAA particles had significantly larger MMADs because many undissolved drug particles were contained within each droplet following actuation. After evaporation of the liquid continuous phase, the suspended drug aggregated to form larger agglomerates than those particles precipitated from the BMV pMDI solution droplets. The addition of a spacer device lowered the MMAD to less than 4.7 microm for particles from both the BMV pMDI solution and the TAA pMDI suspension. The addition of a spacer device also lowered the percentage drug deposited in the induction port. The FPF was significantly increased when a spacer device was used. The MMAD significantly decreased when a spacer device was added for the two model drugs when using the 150-microl metering valves, but the difference was not statistically significant when the 50-microl valves were used (P < .05). The GSD was not influenced by the use of a spacer device. The use of a spacer device will enhance pMDI therapy by reducing the amount of drug deposited in the oropharyngeal region, which will lead to fewer instances of local and systemic side effects. In addition, the spacer devices investigated will allow a higher dose of drug to reach the deep lung, which may permit the use of lower dosage regimens with increased therapeutic efficacy.

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Section: Spacer Devices For Pressurized Metered Dose Inhalers 403mentioning

confidence: 98%

Investigation of Some Commercially Available Spacer Devices for the Delivery of Glucocorticoid Steroids from a pMDI

Williams¹,

Patel²,

Barron

et al. 2001

Drug Development and Industrial Pharmacy

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show abstract

“…The pressurized metered dose inhaler (MDI) has been the cornerstone of asthma maintenance therapy for several decades, but delivers only a small percentage of the drug dose directly into the lungs, with the majority of the dose being deposited in the oropharynx. [1][2][3] The MDI thus confers poor selectivity of drug deposition, which may increase the incidence of both local and systemic side effects for high dose inhaled corticosteroids. 4 The use of a spacer attachment to the MDI may reduce the incidence of these side effects.…”

Section: Introductionmentioning

confidence: 99%

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

Newman¹,

Steed²,

Reader

et al. 1996

Journal of Pharmaceutical Sciences

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In order to provide asthmatic patients with an inhaler that does not use chlorofluorocarbon propellants, a novel multidose hand-held nebulizer (RESPIMAT, Boehringer Ingelheim Ltd.) has been developed. This device delivers 200 x 15 microL metered doses of drug solution, but does not use propellants of any kind. In this study of 10 healthy volunteers, the deposition pattern in the lungs and oropharynx of an ethanolic solution of flunisolide delivered via a prototype III multidose nebulizer has been determined by gamma scintigraphy. A comparison was made with the same dose (250 micrograms) of flunisolide delivered by a pressurized metered dose inhaler (MDI) and MDI plus Inhacort spacer. Mean (SD) whole lung deposition from the multidose nebulizer (39.7 (9.9) % of the metered dose) was significantly higher than that from either MDI (15.3 (5.1) %, P < 0.01) or MDI plus spacer (28.0 (7.0) %, P = 0.01). A mean 10.4% of the dose was recovered from an exhaled air filter for the multidose nebulizer, but less than 2% of the dose for MDI or MDI plus spacer. Oropharyngeal deposition was significantly reduced for the multidose nebulizer (39.9 (9.4) %) compared to MDI (66.9 (7.1) %), but was reduced further for the MDI plus spacer (27.3 (11.3) %). The multidose nebulizer delivers an unusually high percentage of an aerosol dose to the lungs, and it "targets" flunisolide to the lungs more effectively than the MDI. The multidose nebulizer could constitute a viable alternative to MDIs in asthma maintenance therapy.

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“…6,8 Device variables include valve design, 9 metering volume, 5,10 spray orifice diameter, 9 and actuator design. 9,11 In the following series of experiments, aerosols were produced from MDIs containing lecithin microemulsions, and the MMAD, geometric standard deviation (GSD), and FPF (collectively referred to as "aerosol production parameters") of the aerosols were determined by cascade impaction. Experiments were conducted to determine the effect of propellant composition, water content, storage time, and temperature cycling on the aerosol production parameters of MDIs containing lecithin inverse microemulsions.…”

Section: Introductionmentioning

confidence: 99%

Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

Sommerville

Hickey

2003

AAPS PharmSciTech

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Water soluble compounds were incorporated into metered-dose inhalers (MDIs) by using water-in-propellant lecithin microemulsions, in which dimethyl ether (DME) and propane acted as both continuous phase and propellant. Lecithin, water, and water soluble compounds were added to glass MDI containers, valves were crimped on, and propellants were added using a pressure burette. Aerosols were produced using commercially available actuators, and inertial impaction was used to determine the mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction (FPF) of the resulting aerosols. The DME/propane/lecithin microemulsion MDIs generated aerosols with particle size distributions suitable for pulmonary delivery (eg, MMAD 3.1 µm, FPF 59% for DME with lecithin content 3%, water content 2.5% [wt/wt]). Increasing water concentration (up to 8% wt/wt) was correlated with a reduction in FPF. Freezing and rewarming had no adverse effect on MMAD, GSD, or FPF. Storage of microemulsion samples for up to 3 weeks did not adversely affect the MMAD, GSD, or FPF. This approach may enable the pulmonary delivery of water soluble therapeutic agents via MDIs.

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Effect of extension devices on the drug deposition from inhalation aerosols

Cited by 39 publications

References 10 publications

Investigation of Some Commercially Available Spacer Devices for the Delivery of Glucocorticoid Steroids from a pMDI

Investigation of Some Commercially Available Spacer Devices for the Delivery of Glucocorticoid Steroids from a pMDI

Efficient Delivery to the Lungs of Flunisolide Aerosol From a New Portable Hand-Held Multidose Nebulizer

Aerosol generation by metered-dose inhalers containing dimethyl ether/propane inverse microemulsions

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