The Relationship Between Powder Inhaler Resistance and Peak Inspiratory Conditions in Healthy Volunteers — Implications for <i>In Vitro</i> Testing

Clark, AR; Hollingworth, AM

doi:10.1089/jam.1993.6.99

Cited by 307 publications

(196 citation statements)

References 1 publication

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…A coarse grid in the mouthpiece serves to allow only powder to escape from the device. The specific airflow resistance of the Aerolizer® is 0.055 cmH 2 O 1/2 ·L -1 ·min -1 [12].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer

Nielsen¹,

Skov²,

Klug³

et al. 1997

Eur Respir J

View full text Add to dashboard Cite

The output and size distribution of aerosols from dry powder inhalers are dependent on the flow rate through the device. Therefore, in an in vivo study, we examined the flow-dependency of the effect of formoterol when delivered from a dry powder inhaler, the Aerolizer®, in a flow range relevant to schoolchildren.In a preliminary study comprising 126 asthmatic children aged 3-10 yrs, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer® was determined. Mean PIF was 104 L·min -1 and all children aged >5 yrs performed a PIF >60 L·min -1 . Sixteen children aged 8-15 yrs with exercise-induced asthma (EIA) took part in the main trial comparing the protective effect of 12 µg formoterol inhaled at 60 and 120 L·min -1 . The effect from high and low inspiratory flow was judged from the protective effect against EIA 12 h after drug administration.The decrease in forced expiratory volume in one second (FEV1) after exercise was 34% on the placebo day, but only 15% when formoterol was inhaled at the high flow rate. This difference was statistically significant. The decrease in FEV1 was 23% after treatment with formoterol inhaled at the low flow rate, that was not significantly different from placebo or from high-flow formoterol treatment. These clinical findings correspond with the in vitro findings of flow-dependent fine particle mass from the Aerolizer®, and corroborate the relationship between fine particle mass of aerosol and clinical effect.The results indicate a flow-dependent effect of formoterol dry powder inhaled from the Aerolizer®, within the range of inspiratory flow rate obtainable by schoolchildren. This questions its applicability in children with asthma. Eur Respir J 1997; 10: 2105-2109 Formoterol is a highly potent, selective β 2 -agonist producing bronchodilatation of rapid onset [1] and long duration [2][3][4][5]. Inhalation of formoterol (12 µg), both from pressurized aerosol and from dry powder, has been shown to provide children with clinically significant protection against methacholine induced bronchoconstriction [4] and exercise-induced asthma (EIA) [6,7] for at least 12 h.The major advantage of dry powder inhalers (DPIs) is the avoidance of propellants and lubricants, and the fact that they are actuated when the child is inhaling through the device [8,9], thereby overcoming the problem of co-ordination. Formoterol dry powder is delivered from a single-dose dry powder capsule inhaler, the Aerolizer® [10], previously known as the ISF device (ITALSEBER Farmaceutici Italy). The powder comprises micronized active substance and lactose, which serves as a bulking agent. The major disadvantage of DPIs is that the size distribution of the aerosol is dependent on the flow rate through the device, which depends on the internal resistance of the device and the effort of the child. Such effort dependency varies between the DPIs available [11].The objective of this trial was to perform an in vivo study of flow-dependency of the effect of formoterol when delivered from t...

show abstract

“…A coarse grid in the mouthpiece serves to allow only powder to escape from the device. The specific airflow resistance of the Aerolizer® is 0.055 cmH 2 O 1/2 ·L -1 ·min -1 [12].…”

Section: Methodsmentioning

confidence: 99%

“…A coarse grid in the mouthpiece serves to allow only powder to escape from the device. The specific airflow resistance of the Aerolizer® is 0.055 cmH 2 O 1/2 ·L -1 ·min -1 [12].The study was performed in two parts. In a preliminary study, the relationship between age and peak inspiratory flow (PIF) rate through the Aerolizer® was assessed.…”

mentioning

confidence: 99%

Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer

Nielsen¹,

Skov²,

Klug³

et al. 1997

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…The internal "force" required for fluidization and deaggregation is dependent on the resistance of the DPI device and the patient's inspiratory effort (9). Thus, for the purpose of increasing the likelihood of establishing comparable in vitro performance and in vivo drug deposition, the specific resistance of a test device should be comparable to the reference device.…”

Section: Introductionmentioning

confidence: 99%

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

Shur

Lee

Adams

et al. 2012

AAPS J

View full text Add to dashboard Cite

Abstract. This study investigated the effect of modifying the design of the Cyclohaler on its aerosolization performance and comparability to the HandiHaler at multiple flow rates. The Cyclohaler and HandiHaler were designated as model test and reference unit-dose, capsule-based dry powder inhalers (DPIs), respectively. The flow field, pressure drop, and carrier particle trajectories within the Cyclohaler and HandiHaler were modeled via computational fluid dynamics (CFD). With the goal of achieving in vitro comparability to the HandiHaler, the CFD results were used to identify key device attributes and to design two modifications of the Cyclohaler (Mod 1 and Mod 2), which matched the specific resistance of the HandiHaler but exhibited different cyclonic flow conditions in the device. Aerosolization performance of the four DPI devices was evaluated by using the reference product's capsule and formulation (Spiriva capsule) and a multistage cascade impactor. The in vitro data showed that Mod 2 provided a closer match to the HandiHaler than the Cyclohaler and Mod 1 at 20, 39, and 55 l/min. The in vitro and CFD results together suggest that matching the resistance of test and reference DPI devices is not sufficient to attain comparable aerosolization performance, and the improved in vitro comparability of Mod 2 to the HandiHaler may be related to the greater degree of similarities of the flow rate of air through the pierced capsule (Q c ) and the maximum impact velocity of representative carrier particles (V n ) in the Cyclohaler-based device. This investigation illustrates the importance of enhanced product understanding, in this case through the CFD modeling and in vitro characterization of aerosolization performance, to enable identification and modification of key design features of a test DPI device for achieving comparable aerosolization performance to the reference DPI device.KEY WORDS: computational fluid dynamics; device design; dry powder inhaler; in vitro comparability; in vitro performance.

show abstract

“…112 This occurs due to different internal resistance to airflow and a range differentiation from low to high resistance. 113,114 Failure to use the device properly is a common error and therefore a dose is not delivered promptly. 115 Dry powder inhalers with high resistance provide increased deposition to the lung parenchyma, 113,116 but the clinical significance of this remains to be clarified.…”

Section: Dry Powder Inhalersmentioning

confidence: 99%

Inhaled chemotherapy in lung cancer: future concept of nanomedicine

Zarogoulidis

Chatzaki²,

Porpodis³

et al. 2012

IJN

167

160

View full text Add to dashboard Cite

Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

show abstract

The Relationship Between Powder Inhaler Resistance and Peak Inspiratory Conditions in Healthy Volunteers — Implications for In Vitro Testing

Cited by 307 publications

References 1 publication

Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer

Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer

Effect of Device Design on the In Vitro Performance and Comparability for Capsule-Based Dry Powder Inhalers

Inhaled chemotherapy in lung cancer: future concept of nanomedicine

Contact Info

Product

Resources

About