The optimal particle size for parasympathicolytic aerosols in mild asthmatics

Zanen, Pieter; Go, L. T.; Lammers, Jan‐Willem J.

doi:10.1016/0378-5173(94)00224-s

Cited by 51 publications

(22 citation statements)

References 7 publications

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“…The results of the first of the investigations, by Usmani et al, 83 differed from those of Zanen et al, [79][80][81] because bronchodilator response was found to be higher for 3 μm and 6 μm aerosols than for the 1.5 μm aerosol. However, in a follow-up study, bronchodilator response increased with increasing particle size at an inhaled flow rate of 30 L/min but decreased with increasing particle size at an inhaled flow rate of 67 L/min ( Figure 6).…”

Section: Monodisperse Pharmaceutical Aerosol Studiescontrasting

confidence: 55%

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In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

2007

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The purpose of this review is to discuss the roles of cascade impactor (CI) data in inhaler assessment and to examine the relationship between aerodynamic particle size distribution (APSD) and the clinical response to inhaled drugs. A systematic literature search of studies linking APSD to clinical response was undertaken. Two distinct roles for CI-generated data were identified: (1) the control of inhaler/drug product quality; and (2) the provision of data that may be predictive of particle deposition in the respiratory tract. Method robustness is required for the former application, combined with simplicity in operation, resulting in rudimentary attempts to mimic the anatomy of the respiratory tract. The latter necessitates making the apparatus and its operation more closely resemble patient use of the inhaler. A CI cannot perfectly simulate the respiratory tract, since it operates at constant flow rate, while the respiratory cycle has a varying flow-time profile. On the basis of a review of studies linking APSD to clinical response of inhaled drugs, it is concluded that attempts to use CIgenerated data from quality control testing to compare products for bioequivalence are likely to have only limited success, as links between laboratory-measured APSD, particle deposition in the respiratory tract, and clinical response are not straightforward.

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Section: Monodisperse Pharmaceutical Aerosol Studiescontrasting

confidence: 55%

“…In 3 studies, monodisperse bronchodilator aerosols of diameters 1.5 μm, 2.8 μm, and 5.0 μm were compared. [79][80][81] These articles suggest that the optimal bronchodilator particle size in mild asthmatics is ≤ 3 μm and in severe asthmatics is around 3 μm.…”

Section: Monodisperse Pharmaceutical Aerosol Studiesmentioning

confidence: 99%

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

2007

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“…2 differences due to particle size of the aerosol, type of drug, and interaction between drug and aerosol size were determined using repeated measurements analysis of variance (ANOVA).7 A significant interaction, in this case, means that the difference between salbutamol and ipratropium bromide is not constant and depends on the particle size of the aerosol administered. When a statistically significant change was observed, the within group mean sum of squares was used to calculate the least significant difference.…”

Section: Patientsmentioning

confidence: 99%

Optimal particle size for beta 2 agonist and anticholinergic aerosols in patients with severe airflow obstruction.

Zanen¹,

Go²,

Lammers³

1996

Thorax

122

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Background -The optimal particle size of a P2 agonist or anticholinergic aerosol in patients with severe airflow obstruction is unknown. Methods -Seven stable patients with a mean forced expiratory volume in one second (FEV1) of 37.9% of the predicted value inhaled three types of monodisperse salbutamol and ipratropium bromide aerosols with particle sizes of 1.5 gm, 2.8 rtm, and 5 gm, respectively, and a placebo aerosol. The volunteers inhaled 20 ftg salbutamol and 8 ftg ipratropium bromide, after which lung function changes were determined and analysed with repeated measurements analysis of variance (ANOVA). Results -Greater improvements in FEV1, specific airway conductance (sGaw) and maximum expiratory flow at 75%150% of the forced vital capacity (MEF75/50) were induced by the 2.8 gm aerosol than by the other particle sizes. Conclusions -In patients with severe airflow obstruction the particle size of choice for a 2 agonist or anticholinergic aerosol should be approximately 3 ftm.(Thorax 1996;51:977-980) Keywords: aerosols, particle size, bronchodilators. the greatest bronchodilatation.4 To reach the smaller airways in such cases it may be necessary for the particle size of the inhaled aerosol to be decreased. In patients with severe airflow obstruction, aerosols with a smaller particle size may be more suitable. We therefore carried out experiments to determine the most suitable particle size for bronchodilator aerosols in patients with severe airflow obstruction. Methods PATIENTSEight patients (six men) started the trial but one dropped out for personal reasons. The mean (SD) age of the remaining seven was 55 (4) years, and the mean forced expiratory volume in one second (FEVI) was 37.9 (7.3)% of the predicted value. In all patients a more than 15% increase in baseline FEV1 after inhalation of 200 jg salbutamol had been measured just before the trial. None of the patients was smokers. All used inhaled corticosteroids and none used disodium cromoglycate or oral antiasthma medications. Their regular medication other than corticosteroids was discontinued 6-8 hours before the start of the trial, and long acting 12 agonists were stopped 15 hours before the trial. All patients gave their written consent before entry into the study which was approved by the hospital ethics committee.

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“…A limited number of studies have been published about the relationship between mass median aerodynamic diameter and deposition patterns in the lung, but these have involved small numbers of subjects, showed limitations in methodology, and occasionally led to discrepant conclusions. [19][20][21][22] Thus, currently there is no predictive relationship between changes in APSD and clinical results. Without a clinically defined "permitted difference" or a "gold standard" to which the outcome of the statistical procedure could be compared, the experienced judgment of the WG members using "target profiles" described previously 7 was the best available option.…”

Section: E7mentioning

confidence: 99%

Product quality research institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 3: Final report on a statistical procedure for determining equivalence

Christopher¹,

Adams

Amann³

et al. 2007

AAPS PharmSciTech

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The purpose of this article is to report final results of the evaluation of a chi-square ratio test proposed by the US Food and Drug Administration (FDA) for demonstrating equivalence of aerodynamic particle size distribution (APSD) profiles of nasal and orally inhaled drug products. A working group of the Product Quality Research Institute previously published results demonstrating some limitations of the proposed test. In an effort to overcome the test's limited discrimination, the group proposed a supplemental test, a population bioequivalence (PBE) test for impactor-sized mass (ISM). In this final report the group compares the chi-square ratio test to the ISM-PBE test and to the combination of both tests. The basis for comparison is a set of 55 realistic scenarios of cascade impactor data, which were evaluated for equivalence by the statistical tests and independently by the group members. In many instances, the combined application of these 2 tests appeared to increase the discriminating ability of the statistical procedure compared with the chi-square ratio test alone. In certain situations the chi-square ratio test alone was sufficient to determine equivalence of APSD profiles, while in other situations neither of the tests alone nor their combination was adequate. This report describes all of these scenarios and results. In the end, the group did not recommend a statistical test for APSD profile equivalence. The group did not investigate other in vitro tests, in vivo issues, or other statistical tests for APSD profile comparisons. The studied tests are not intended for routine quality control of APSD.

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The optimal particle size for parasympathicolytic aerosols in mild asthmatics

Cited by 51 publications

References 7 publications

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

In vitro and in vivo aspects of cascade impactor tests and inhaler performance: A review

Optimal particle size for beta 2 agonist and anticholinergic aerosols in patients with severe airflow obstruction.

Product quality research institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 3: Final report on a statistical procedure for determining equivalence

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