Evaluation of Probability Density Functions to Approximate Particle Size Distributions of Representative Pharmaceutical Aerosols

Dunbar, Craig; Hickey, Anthony

doi:10.1016/s0021-8502(99)00557-1

Cited by 59 publications

(40 citation statements)

References 10 publications

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“…Evaluation of GSD is valid only if the aerosol particle size distribution is log-normal. 20 The FPD is the total mass of particles in the aerosol that have aerodynamic diameters less than ~5 µm. The emitted dose was calculated as the ex-actuator emitted dose (i.e., spacer deposition is included) to enable meaningful comparisons between spacer and no-spacer experiments.…”

Section: Discussionmentioning

confidence: 99%

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

Smyth¹,

Beck²,

Williams³

et al. 2004

AAPS PharmSciTech

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INTRODUCTIONThe purpose of this study was to evaluate the hypothesis that spacer devices have limited effect on the in vitro fine particle dose emitted from solution metered dose inhalers containing different proportions of HFA134a [1,1,1,2,-tetrafluoroethane] propellant. Two solution formulations (80% and 97.5% wt/wt HFA134a) were tested across the actuator alone, actuator plus Aerochamber, and Ace holding chamber. Particle size distributions were determined using laser diffraction (LD) and cascade impaction (CI). Multimodal particle size distributions were identified using LD. CI analyses were characterized by a major mode located at ~0.5 µm. The fine particle dose emitted from the inhaler spacer combinations containing 97.5% HFA134a was independent of the device setup used. Fine particle doses were influenced by spacer setup in 80% HFA134a formulations, indicating different plume dynamics of low vapor pressure formulations. Sampling inlet deposition was approximately 0 when spacer devices were used with either formulation. When spacers were not used, sampling inlet deposition was increased significantly. However, inlet deposition with the 97.5% HFA134a formulation was significantly less than that of the 80% HFA134a formulation (~25% of emitted dose compared with 69%, respectively). Thus, high propellant concentration formulations appear to have more robust in vitro performance. This is particularly important given the preponderance of poor patient compliance that is associated with spacer use. High propellant concentrations had the advantage of fine particle doses that were independent of the device setup and significantly lowered sampling inlet deposition when no spacer was used.Pressurized metered dose inhalers (pMDIs) have proved an effective means of administering drugs to respiratory tract in the treatment and management of asthma. 1 However, reproducibility of dosing has been a concern with these devices because of noncompliance in prescribed usage. 2 Accurate dosing is especially necessary in cases where immediate pharmacodynamic feedback is not useful for dosage regulation, as in the case for corticosteroids employed for longterm maintenance therapy for asthma. Dose-related systemic side effects occur secondary to absorption of drug from mouth, throat, gastrointestinal tract, and lungs. Variability in dosing may result in too much or, more significantly, too little drug being delivered, with consequences for disease management. Noncompliant use of pMDIs is associated with the difficulty of inhalation-actuation coordination (particularly for children and elderly users). 3 As a consequence, devices such as spacers have been developed for use with pMDIs to improve dosing reproducibility and reduce unwanted oral deposition of aerosol droplets. 4 Spacers function by reducing the aerosol velocity, allowing time for evaporation and sedimentation, thus reducing deposition of large particles in the mouth and throat. 4 Additionally, it has been shown that spacers increase the fine particle dose (FPD) t...

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Section: Discussionmentioning

confidence: 99%

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

Smyth¹,

Beck²,

Williams³

et al. 2004

AAPS PharmSciTech

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“…Particle size distributions can be represented in two forms, as a Probability Density Function (PDF) or as a Cumulative Distribution Function (CDF). Normally, an independent variable (x) and two more adjustable parameters, representing the particle size and the distribution of particle sizes are used [20]. There are several types of mathematical distributions to describe spray particles/droplets, being the Log-Normal, Rosin-Rammler and NukiyamaTanasawa, the most common.…”

Section: Droplet Size Distributionsmentioning

confidence: 99%

“…They concluded that the best fitting method is through the nonlinear least squares of the PDF and that the Log-Normal and Nukiyama-Tanasawa PDFs produced better fitting results to the data than the Rosin-Rammler function [20].…”

Section: Droplet Size Distributionsmentioning

confidence: 99%

“…The Ventolin® most important characteristics for the simulation are listed in The particle size data were measured using the laser diffraction technique, using an independent model for data processing. Data were fitted to the cumulative function of Rosin-Rammler distribution, using the least squares method [20]. The CFD solver accepts this distribution type by inserting its corresponding parameters, see …”

Section: Drug Properties and Spray Characterisationmentioning

confidence: 99%

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pMDI Sprays: Theory, Experiment and Numerical Simulation

Oliveira¹,

Teixeira²,

Teixeira³

et al. 2012

Advances in Modeling of Fluid Dynamics

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“…Such types of stochastic systems are called Stochastic Distribution Control (SDC) systems [5]. Practical examples of SDC systems in industrial applications include: Molecular weight distribution control [7], [8], combustion flame distribution processes [9], [10], particle size distribution control in polymerisation and powder processing industries [11], [12], and the wet-end of paper-making [5].…”

Section: Introductionmentioning

confidence: 99%

Fault detection and diagnosis for general discrete-time stochastic systems using output probability density estimation

Skaf

AI-Bayati

Wang

2011

IEEE Conference on Decision and Control and European Control Conference

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Abstract-A new approach of fault detection and diagnosis (FDD) for general stochastic systems in discrete-time is studied. Our work on this problem is motivated by the fact that most of the nonlinear control laws are implemented as digital controllers in reality. Different from the formulation of classical FDD problem, it is supposed that the measured information for the FDD is the probability density functions (PDFs) of the system output rather than its measured value. A radial basis function (RBF) neural network technique is proposed so that the output PDFs can be formulated in terms of the dynamic weighting of the RBFs neural network. Feasible criteria to detect and diagnose the system fault are provided by using linear matrix inequality (LMI) techniques. An illustrated example is included to demonstrate the efficiency of the proposed algorithm, and satisfactory results are obtained.

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Evaluation of Probability Density Functions to Approximate Particle Size Distributions of Representative Pharmaceutical Aerosols

Cited by 59 publications

References 10 publications

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

The influence of formulation and spacer device on the in vitro performance of solution chlorofluorocarbon-free propellant-driven metered dose inhalers

pMDI Sprays: Theory, Experiment and Numerical Simulation

Fault detection and diagnosis for general discrete-time stochastic systems using output probability density estimation

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