Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer

Abstract

In the treatment of asthma, inhaled formulations are commonly used to direct drugs to the lungs. The inhaled drug is deposited either in the upper respiratory tract or in the lungs. Exhaled drug generally constitutes a negligible part of the dose. The fraction deposited extrapulmonarily is eventually swallowed and absorbed from the gastrointestinal (GI) tract and will thus contribute to the systemic availability of the inhaled drug.Spacer devices between the actuator and the mouth are used to overcome the problem of co-ordinating actuation and inhalation from a pressurized metered-dose inhaler (pMDI). The particle size in the aerosol is reduced as evaporation of the propellant occurs [1][2][3]. Also, larger particles are preferentially deposited on the walls of the spacer. An increased fraction of small particles means that deposition in the oropharynx is decreased. In addition, lung deposition may be increased due to the fact that the velocity of the aerosol cloud is reduced before inhalation.The Nebuhaler® is a large-volume (750 mL) spacer intended for pMDIs of budesonide and terbutaline sulphate. Studies with 99m Tc-labelled Teflon™ particles, using γ-scintigraphic imaging techniques, have shown that the lung deposition, in asthmatic patients with airflow obstruction, increased from approximately 9% of the metered dose with a pMDI alone, to 21% after a single puff and 15% after multiple puffs when the pMDI was attached to a Nebuhaler® [4]. The lung deposition of 99m Tc-labelled terbutaline sulphate from a pMDI with a Nebuhaler® was 32% compared with 11% from a pMDI alone [5].Scintigraphic imaging is a commonly used technique to determine lung deposition after inhalation. Lung deposition can also be determined from urinary excretion of intact drug, provided that the contribution of orally deposited and subsequently swallowed drug can be accounted for, and that the drug is not metabolized in the lung [6]. One approach to accounting for swallowed drug is to prevent GI absorption by using concomitant oral administration of activated charcoal [7]. Another approach is to calculate the lung deposition from the systemic availability after inhalation by subtracting the estimated oral contribution [7].Budesonide is a potent glucocorticosteroid effective in the treatment of asthma. When given by inhalation, its antiasthmatic effect may be explained by a local pulmonary action [8]. No oxidative or reductive metabolism of budesonide has been noted in human lung homogenates [9]. The drug is rapidly and extensively absorbed [10]. Pharmacokinetic studies, performed in healthy subjects and asthmatic children, have shown that budesonide undergoes a high first-pass metabolism and has a low systemic availability (about 10%) after oral dosing [10,11]. Inhaled budesonide undergoes a rapid systemic uptake, with a time of maximum concentration of about 20 min. The systemic availability was found to be 26% from a pMDI and 38% Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer. L. Thorsson, S. E...

Switching from branded to generic inhaled medications: potential impact on asthma and COPD

“…However, Chang et al [25] administered both salbutamol formulations using pMDIs in conjunction with spacers, thus affecting drug deposition, and consequently, the effectiveness of both preparations. An earlier study showed that failure to shake the canister before each inhalation halved the systemic availability of budesonide from a pMDI compared with that from the pMDI used with a spacer [26], confirming that suboptimal usage can have a profound effect on drug delivery from a pMDI and that use of a spacer can mitigate this variability [26].…”

Dose-response relationship of inhaled budesonide in adult asthma: a meta-analysis

“…To be included in the primary meta-analysis, studies had to meet all of the following criteria: a double-blind, placebo-controlled, randomised trial involving two or more doses of budesonide, delivered by turbuhaler or metered-dose inhaler (MDI)zspacer device twice daily, in adolescents (agedw12 yrs) or adults with asthma, of at least 4 weeks in duration. The decision to include studies using the turbuhaler and MDIzspacer was based on evidence that both delivery systems achieved similar lung deposition, greater than that with the MDI alone [6,7], although it is noted that a formal dose-response comparison between the two devices was not undertaken. The search strategy recommended by the QUORUM statement is shown in figure 1. Letters were sent to the authors of three out of six studies included in the metaanalysis to obtain the data in the format required.…”

Drug Delivery from an Innovative LAMA/LABA Co-suspension Delivery Technology Fixed-Dose Combination MDI: Evidence of Consistency, Robustness, and Reliability

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