A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions.

  title={A theoretical and experimental analysis of formulation and device parameters affecting solution MDI size distributions.},
  author={Stephen W. Stein and Paul Myrdal},
  journal={Journal of pharmaceutical sciences},
  volume={93 8},
  • S. Stein, P. Myrdal
  • Published 1 August 2004
  • Chemistry, Medicine
  • Journal of pharmaceutical sciences
The influence of formulation and device configurations on the initial droplet and residual particle size distribution from solution MDIs was theoretically and experimentally examined. Aerodynamic size distribution tests were conducted to characterize the size distribution of the residual particles formed when a solution MDI is actuated. The measured size distributions were approximately log-normally distributed, and did not show evidence of a secondary large particle mode. Theoretical… 
The influence of initial atomized droplet size on residual particle size from pressurized metered dose inhalers.
The relationship between APSDR and drug concentration and MMDI is predictable for solution pMDIs, but this is not as straightforward for suspension formulations; however, there are situations in which hypothetically small micronized drug in suspension could resemble trends observed for solution formulations.
The Formation of Aerosol Particles from Solution-Based Pressurized Metered Dose Inhalers and Implications of Incomplete Droplet Drying: Theoretical and Experimental Comparison
The aerosol particle size distributions of solution-based pressurized metered dose inhalers containing 15%w/w ethanol and different quantities of nonvolatile component (NVC) (drug and glycerol) were
A model for predicting size distributions delivered from pMDIs with suspended drug.
A new model has been developed for predicting size distributions delivered from pressurized metered dose inhalers (pMDIs) that contain suspended drug particles. This model enables the residual
Transient aerodynamic atomization model to predict aerosol droplet size of pressurized metered dose inhalers (pMDI)
ABSTRACT Pressurized metered dose inhalers (pMDI) produce large numbers of droplets with smaller sizes than 5 μm to treat asthma and other pulmonary diseases. The mechanism responsible for droplet
Tuning Aerosol Particle Size Distribution of Metered Dose Inhalers Using Cosolvents and Surfactants
The findings highlight the different mechanisms by which these components influence droplet formation and demonstrate the ability to utilize the different effects in formulations of pMDI-HFA 227 for independently modulating particle sizes in the respirable region.
Impact of droplet evaporation rate on resulting in vitro performance parameters of pressurized metered dose inhalers.
It was demonstrated that throat deposition, cascade impactor deposition, FPF, and mass median aerodynamic diameter of solution pMDIs depend on the concentration and vapor pressure of the cosolvent, and the selection of model throat, indicating that evaporation kinetics significantly influences pMDI drug delivery.
Investigation of influence factors on particle size measurement with pMDI
These factors (environmental temperature and humidity, flow rate, and device temperature) had significant influence on the performance of LD or NGI, and should be controlled in the particle size measurement of pMDI.
Estimating the Number of Droplets and Drug Particles Emitted from MDIs
  • S. Stein
  • Medicine, Chemistry
    AAPS PharmSciTech
  • 2007
The number of particles in MDI aerosols was shown to be highly dependent on the mass median aerodynamic diameter (MMAD) and geometric standard deviation, and to a lesser extent the total mass of the aerosol.
Modeling and Understanding Combination pMDI Formulations with Both Dissolved and Suspended Drugs.
A simulation model has been established to predict the residual aerodynamic particle size distribution (APSD) of dual-component pressurized metered dose inhalers (pMDIs) and demonstrates that this model is a useful tool that may be able to expedite the development of combination pMDI formulation.
The solid-state and morphological characteristics of particles generated from solution-based metered dose inhalers: Influence of ethanol concentration and intrinsic drug properties
Abstract The aerosol performance, physical properties and formation process of two corticosteroids (beclomethasone dipropionate and fluticasone propionate) and caffeine (active pharmaceutical


An Evaluation of Mass-Weighted Size Distribution Measurements with the Model 3320 Aerodynamic Particle Sizer
The ability of the Model 3320 aerodynamic particle sizer (APS) to make accurate mass-weighted size distribution measurements was investigated. Significant errors were observed in APS size
Concentration measurement and counting efficiency for the aerodynamic particle sizer 3320
Abstract The aerodynamic particle sizer (APS, Model 3320, TSI Inc., St. Paul, MN) is an instrument that counts and sizes particles by time-of-flight, an aerodynamic property, and/or by
Evaluation of a new Aerodynamic Particle Sizer Spectrometer for size distribution measurements of solution metered dose inhalers.
The ability of the Model 3320 and newer Model 3321 Aerodynamic Particle Sizer Spectrometer (APS) to make accurate mass-weighted size distribution measurements of solution metered dose inhalers (MDIs) was evaluated and was shown to be proportional to drug concentration to the one-third power.
Influence of formulation on aerosol particle size.
A cascade impactor was employed to measure aerosol particle size in a study designed to investigate the influence of several formulation parameters on aerosol particle size. Laboratory data indicate
Droplet breakup phenomena in flows with velocity lag
Abstract Available experimental data on droplet disintegration have been reviewed with due regard for modern knowledge of the phenomenon. Disintegration processes are known to be induced in flows
Concentration measurement and counting e ciency of the aerodynamic particle sizer 3321
The aerodynamic particle sizer (APS) model 3321 (TSI, Inc., St. Paul, MN) aims to resolve issues identi3ed with an earlier APS, model 3320. These issues include discrepancies between concentrations
Balancing ethanol cosolvent concentration with product performance in 134a-based pressurized metered dose inhalers.
  • Abhishek Gupta, S. Stein, P. Myrdal
  • Chemistry, Medicine
    Journal of aerosol medicine : the official journal of the International Society for Aerosols in Medicine
  • 2003
The MRM represents the maximum amount of a given drug that can be delivered to the lungs theoretically and is very sensitive to the solubility profile of the drug.
Theoretical relationship of lung deposition to the fine particle fraction of inhalation aerosols.
Under well defined conditions there appeared to be a qualitative correlation between respirable fraction and predicted lower lung deposition, however, this was influenced by the aerosol particle size distribution and breathing parameters.
Entry Port Selection for Detecting Particle Size Differences in Metered Dose Inhaler Formulations Using Cascade Impaction
The 1 L entry port was further compared with the USP entry port in its ability to discriminate between subtle changes in particle size distribution (PSD) in an investigational hydrofluoroalkane (HFA)‐based MDI formulation.
Comparison of the TSI Model 3306 Impactor Inlet with the Andersen Cascade Impactor: Solution Metered Dose Inhalers
For formulations containing 10–20% w/w ethanol it is shown that an extension fitted to the Model 3306 yielded an improved correlation to those obtained from the ACI, which was found that good correlations between the two instruments were obtained.