Study of pressurised metered dose inhalers for the purpose of standardization of quality attributes characterizing uniformity of dosing

Authors

DOI:

https://doi.org/10.15587/2519-4852.2021.238294

Keywords:

pressurized metered dose inhaler, particle size, dose mass, delivered dose, fine particle dose, uniformity, procedure, validation

Abstract

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

Author Biographies

Elena Bezuglaya, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Senior Researcher, Head of Laboratory

Laboratory of Technology and Analysis of Medicinal Products

Nikolay Lyapunov, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

Doctor of Pharmaceutical Sciences, Professor, Leading Researcher

Laboratory of Technology and Analysis of Medicinal Products

Vladimir Bovtenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Junior Researcher

Laboratory of Technology and Analysis of Medicinal Products

Igor Zinchenko, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Junior Researcher

Laboratory of Technology and Analysis of Medicinal Products

Yurij Stolper, State Scientific Institution “Institute for Single Crystals” of National Academy of Sciences of Ukraine

PhD, Senior Researcher

Laboratory of Technology and Analysis of Medicinal Products

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Published

2021-08-31

How to Cite

Bezuglaya, E., Lyapunov, N., Bovtenko, V., Zinchenko, I., & Stolper, Y. (2021). Study of pressurised metered dose inhalers for the purpose of standardization of quality attributes characterizing uniformity of dosing. ScienceRise: Pharmaceutical Science, (4(32), 11–23. https://doi.org/10.15587/2519-4852.2021.238294

Issue

No. 4(32) (2021)

Section

Pharmaceutical Science

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Copyright (c) 2021 Elena Bezuglaya, Nikolay Lyapunov, Vladimir Bovtenko, Igor Zinchenko, Yurij Stolper

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