The Influence of Electrostatic Controls on MDI Size Distribution Measurements

Stein, Stephen W.; Rasmussen, J. B.; Walls, Sheila; Schultz, David; Oakley, C.; Drake, James

doi:10.1208/s12249-019-1354-7

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…Electrostatic charge accumulation can result in highly variable APSD measurement outcomes, which are still poorly understood in comparison with other physical processes associated with aerosol formation by OIPs. Part of the problem is associated with the limited availability of suitable measurement equipment having the capability to make relevant and reproducible measurements (89). Implementation of electrostatic controls, including grounding both the analyst and the equipment, using an ionizing air blower and anti-static gun to discharge the air surrounding the apparatus, and having the analyst not wear gloves or touch the induction port during testing have been shown to be effective for the mitigation of electrostatic charge-related effects in the context of APSD determination with pMDIs (89).…”

Section: Good Cascade Impactor Practicesmentioning

confidence: 99%

“…Part of the problem is associated with the limited availability of suitable measurement equipment having the capability to make relevant and reproducible measurements (89). Implementation of electrostatic controls, including grounding both the analyst and the equipment, using an ionizing air blower and anti-static gun to discharge the air surrounding the apparatus, and having the analyst not wear gloves or touch the induction port during testing have been shown to be effective for the mitigation of electrostatic charge-related effects in the context of APSD determination with pMDIs (89). A further precaution is to undertake the measurements in an ambient environment with controlled relative humidity in excess of 35% (90).…”

Section: Good Cascade Impactor Practicesmentioning

confidence: 99%

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Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs

Mitchell¹,

Doub³

et al. 2019

AAPS PharmSciTech

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The multi-stage cascade impactor (CI) is the mainstay method for the determination of the aerodynamic particle size distribution (APSD) of aerosols emitted from orally inhaled products (OIPs). CIs are designed to operate at a constant flow rate throughout the measurement process. However, it is necessary to mimic an inhalation maneuver to disperse the powder into an aerosol when testing passive dry powder inhalers (DPIs), which constitute a significant portion of available products in this inhaler class. Methods in the pharmacopeial compendia intended for product quality assurance initiate sampling by applying a vacuum to the measurement apparatus using a timer-operated solenoid valve located downstream of the CI, resulting in a period when the flow rate through the impactor rapidly increases from zero towards the target flow rate. This article provides recommendations for achieving consistent APSD measurements, including selection of the CI, pre-separator, and flow control equipment, as well as reviewing considerations that relate to the shape of the flow rate-sampling time profile. Evidence from comparisons of different DPIs delivering the same active pharmaceutical ingredients (APIs) is indicative that the compendial method for APSD measurement is insensitive as a predictor of pharmacokinetic outcomes. Although inappropriate for product quality testing, guidance is therefore provided towards adopting a more clinically realistic methodology, including the use of an anatomically appropriate inlet and mimicking patient inhalation at the DPI while operating the CI at constant flow rate. Many of these recommendations are applicable to the testing of other OIP classes.

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Section: Good Cascade Impactor Practicesmentioning

confidence: 99%

Section: Good Cascade Impactor Practicesmentioning

confidence: 99%

Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs

Mitchell¹,

Doub³

et al. 2019

AAPS PharmSciTech

Self Cite

View full text Add to dashboard Cite

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Addressing the Need for Controls on Particle Bounce and Re-entrainment in the Cascade Impactor and for the Mitigation of Electrostatic Charge for Aerodynamic Particle Size Assessment of Orally Inhaled Products: an Assessment by the International Consortium on Regulation and Science (IPAC-RS)

Doub¹,

Stein

Mitchell³

et al. 2020

AAPS PharmSciTech

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Evaluation of Valved Holding Chambers Simulating Repurposing Use of Ciclesonide Metered-dose Inhaler by Patients with Pneumonia

Yoshida¹,

Abe²,

Usui³

et al. 2020

YAKUGAKU ZASSHI

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Achieving appropriate inhalation in patients with coronavirus disease 2019 (COVID-19) is a common challenge in the use of repurposed metered-dose inhaler (MDI) formulations. The purpose of this study was to evaluate the eŠect of ve valved holding chambers (VHCs) on the inhalation of ciclesonide from Alvesco MDI. The aerodynamic particle size distribution of ciclesonide discharged from Alvesco MDI was evaluated using a Next Generation Impactor in the presence and absence of VHCs. The use of VHCs retained or slightly increased the amount of ciclesonide in theˆne particle diameter range (aerodynamic particle size below 3 mm) (FPD) and reduced the amount at the induction port after coordinated inhalation. However, the use of VHC reduced the FPD of the formulation by increasing the time between the MDI discharge and the pump suction by various degrees among theˆve VHCs. These results indicated that use of the VHCs and minimizing the inhalation delay time should ensure su‹cient inhalation of ciclesonide particles.

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The Influence of Electrostatic Controls on MDI Size Distribution Measurements

Cited by 3 publications

References 16 publications

Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs

Determination of Passive Dry Powder Inhaler Aerodynamic Particle Size Distribution by Multi-Stage Cascade Impactor: International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) Recommendations to Support Both Product Quality Control and Clinical Programs

Addressing the Need for Controls on Particle Bounce and Re-entrainment in the Cascade Impactor and for the Mitigation of Electrostatic Charge for Aerodynamic Particle Size Assessment of Orally Inhaled Products: an Assessment by the International Consortium on Regulation and Science (IPAC-RS)

Evaluation of Valved Holding Chambers Simulating Repurposing Use of Ciclesonide Metered-dose Inhaler by Patients with Pneumonia

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