scholarly journals Tuning Aerosol Particle Size Distribution of Metered Dose Inhalers Using Cosolvents and Surfactants

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Imran Y. Saleem ◽  
Hugh D. C. Smyth

Objectives.The purpose of these studies was to understand the influence of cosolvent and surfactant contributions to particle size distributions emitted from solution metered dose inhalers (pMDIs) based on the propellant HFA 227.Methods.Two sets of formulations were prepared: (a) pMDIs-HFA 227 containing cosolvent (5–15% w/w ethanol) with constant surfactant (pluronic) concentration and (b) pMDIs-HFA 227 containing surfactant (0–5.45% w/w pluronic) with constant cosolvent concentration. Particle size distributions emitted from these pMDIs were analyzed using aerodynamic characterization (inertial impaction) and laser diffraction methods.Results. Both cosolvent and surfactant concentrations were positively correlated with median particle sizes; that is, drug particle size increased with increasing ethanol and pluronic concentrations. However, evaluation of particle size distributions showed that cosolvent caused reduction in the fine particle mode magnitude while the surfactant caused a shift in the mode position. These 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.Conclusion. Potentially, the formulation design window generated using these excipients in combination could be used to match the particle size output of reformulated products to preexisting pMDI products.

2021 ◽  
Vol 94 ◽  
pp. 36-48
Author(s):  
María Liliana Darder ◽  
Antonio Paz-González ◽  
Aitor García-Tomillo ◽  
Marcos Lado ◽  
Marcelo German Wilson

Author(s):  
Elena Bezuglaya ◽  
Nikolay Lyapunov ◽  
Vladimir Bovtenko ◽  
Igor Zinchenko ◽  
Yurij Stolper

Aim. The purpose was to provide the rationale of test in regard to uniformity of fine particles dose for pressurised metered dose inhalers (pMDIs). Materials and methods. The pMDIs containing suspensions of salbutamol sulfate (SS) or solutions of beclometasone dipropionate (BD) were studied by laser diffraction and high performance liquid chromatography (HPLC). The particle size distribution of SS, the average dose mass and uniformity of dose mass, the average delivered dose and the uniformity of delivered dose, the average fine particles dose and uniformity of fine particles dose were determined. Apparatus A was used for assessment of fine particles dose. Results. The two analytical procedures for the quantitative determination of SS and BD by HPLC were validated in the ranges with low concentrations of these substances. The 5 medicinal products in pMDI dosage form were studied: 3 preparations were with SS and 2 ones contained BD. It was shown that three products with SS were very similar in regard to particle size distribution in containers and the average values of delivered dose were almost the same, but these products were different in the average dose mass and fine particle dose. According to the research results, the expediency of determining the average dose mass and the tests concerning uniformity of dosing of preparations by dose mass and by fine particle dose was substantiated. It was shown that in the case of pMDI the dosing of solutions of BD was more uniform compared to suspensions of SS. The approaches of leading and other pharmacopoeias concerning uniformity of dosing for pMDIs were critically discussed. The expediency of determination of uniformity of fine particle dose at the stage of pharmaceutical development was substantiated, as the therapeutic effect depends on fine particle dose. Issues concerning standardization pMDIs in regard to uniformity of fine particle dose were discussed. Conclusions. The expediency of standardization and quality control of pMDIs in regard to such attributes as the average dose mass, which characterizes the volume of the metering chamber of the valve as well as the uniformity of the dose mass and the uniformity of fine particle dose, which assure the therapeutic effect of each dose of the product was substantiated


2018 ◽  
Vol 10 (11) ◽  
pp. 1753 ◽  
Author(s):  
Huige Di ◽  
Qiyu Wang ◽  
Hangbo Hua ◽  
Siwen Li ◽  
Qing Yan ◽  
...  

The use of Raman and high-spectral lidars enables measurements of a stratospheric aerosol extinction profile independent of backscatter, and a multi-wavelength (MW) lidar can obtain additional information that can aid in retrieving the microphysical characteristics of the sampled aerosol. The inversion method for retrieving aerosol particle size distributions and microphysical particle parameters from MW lidar data was studied. An inversion algorithm for retrieving aerosol particle size distributions based on the regularization method was established. Based on the inversion of regularization, the inversion method was optimized by choosing the base function closest to the aerosol distribution. The logarithmic normal distribution function was selected over the triangle function as the base function for the inversion. The averaging procedure was carried out for three main types of aerosol. The 1% averaging result near the minimum of the discrepancy gave the best estimate of the particle parameters. The accuracy and stabilization of the optimized algorithm for microphysical parameters were tested by scores of aerosol size distributions. The systematic effects and random errors impacting the inversion were also considered, and the algorithm was tested by the data, showing 10% systematic error and 15% random error. At the same time, the reliability of the proposed algorithm was also verified by using the aerosol particle size distribution data of the aircraft. The inversion results showed that the algorithm was reliable in retrieving the aerosol particle size distributions at vertical heights using lidar data.


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