Insights into particle formation and analysis

    Tutkimustuotos: OpinnäyteVäitöskirjaArtikkelikokoelma

    Kuvaus

    This thesis consists of two parts, particle formation and analysis. In the first part, particle formation in microfluidic devices and in devices employing supercritical fluids is investigated, and in the second part, essential issues in analytical methods for determining drug release and solid-state properties are addressed. Microfluidic technology was employed to produce microcapsules for protein formulations. The microcapsules were produced with a biphasic flow to create water-oil-water double emulsion droplets with ultrathin shells. All the particles were found to be intact and with a particle size of 23 - 47 µm. The encapsulation efficiency of bovine serum albumin in the microcapsules was 84%. This study demonstrates that microfluidics is a powerful technique for engineering formulations for therapeutic proteins. A new, robust, stable, and reproducible method based on expansion of supercritical solutions using carbon dioxide as a solvent was developed to produce nanoparticles. The method, Controlled Expansion of Supercritical Solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Controlled pressure reduction keeps the particle growth and production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm). The Lyophilic Matrix (LM) method was developed for investigating dissolution rates of nanoparticles, powders, and particulate systems. The LM method is based on its ability to discriminate between non-dissolved particles and the dissolved species. In the LM method, the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while inhibiting dispersion of non-dissolved particles without presenting a substantial diffusion barrier. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. Time-gated Raman spectroscopy was applied for solid-state analysis of fluorescent powder mixtures. A setup with a 128 × (2) × 4 CMOS SPAD detector was used for the quantitative analysis of solid-state forms of piroxicam. Time-gating provides an instrumental method for rejecting the fluorescence signal. This study demonstrated that traditional PLS analysis of time-gated Raman spectra resulted in mean RMSE of 4.1%. The time-gated Raman spectroscopy method shows potential for relatively routine quantitative solid-state analysis of photoluminescent pharmaceuticals.
    Alkuperäiskielienglanti
    Myöntävä instituutio
    • Helsingin yliopisto
    Valvoja/neuvonantaja
    • Yliruusi, Jouko, Valvoja
    • Haeggström, Edward, Valvoja
    • Juppo, Anne, Valvoja
    Myöntöpäivämäärä3 marraskuuta 2017
    JulkaisupaikkaHelsinki
    Kustantaja
    Painoksen ISBN978-951-51-3679-4
    Sähköinen ISBN978-951-51-3680-0
    TilaJulkaistu - 3 marraskuuta 2017
    OKM-julkaisutyyppiG5 Tohtorinväitöskirja (artikkeli)

    Tieteenalat

    • 317 Farmasia

    Lainaa tätä

    Pessi, J. J. (2017). Insights into particle formation and analysis. Helsinki: University of Helsinki.
    Pessi, Jenni Johanna. / Insights into particle formation and analysis. Helsinki : University of Helsinki, 2017. 112 Sivumäärä
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    title = "Insights into particle formation and analysis",
    abstract = "This thesis consists of two parts, particle formation and analysis. In the first part, particle formation in microfluidic devices and in devices employing supercritical fluids is investigated, and in the second part, essential issues in analytical methods for determining drug release and solid-state properties are addressed. Microfluidic technology was employed to produce microcapsules for protein formulations. The microcapsules were produced with a biphasic flow to create water-oil-water double emulsion droplets with ultrathin shells. All the particles were found to be intact and with a particle size of 23 - 47 µm. The encapsulation efficiency of bovine serum albumin in the microcapsules was 84{\%}. This study demonstrates that microfluidics is a powerful technique for engineering formulations for therapeutic proteins. A new, robust, stable, and reproducible method based on expansion of supercritical solutions using carbon dioxide as a solvent was developed to produce nanoparticles. The method, Controlled Expansion of Supercritical Solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Controlled pressure reduction keeps the particle growth and production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm). The Lyophilic Matrix (LM) method was developed for investigating dissolution rates of nanoparticles, powders, and particulate systems. The LM method is based on its ability to discriminate between non-dissolved particles and the dissolved species. In the LM method, the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while inhibiting dispersion of non-dissolved particles without presenting a substantial diffusion barrier. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. Time-gated Raman spectroscopy was applied for solid-state analysis of fluorescent powder mixtures. A setup with a 128 × (2) × 4 CMOS SPAD detector was used for the quantitative analysis of solid-state forms of piroxicam. Time-gating provides an instrumental method for rejecting the fluorescence signal. This study demonstrated that traditional PLS analysis of time-gated Raman spectra resulted in mean RMSE of 4.1{\%}. The time-gated Raman spectroscopy method shows potential for relatively routine quantitative solid-state analysis of photoluminescent pharmaceuticals.",
    keywords = "317 Pharmacy",
    author = "Pessi, {Jenni Johanna}",
    year = "2017",
    month = "11",
    day = "3",
    language = "English",
    isbn = "978-951-51-3679-4",
    series = "Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis",
    publisher = "University of Helsinki",
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    Pessi, JJ 2017, 'Insights into particle formation and analysis', Helsingin yliopisto, Helsinki.

    Insights into particle formation and analysis. / Pessi, Jenni Johanna.

    Helsinki : University of Helsinki, 2017. 112 s.

    Tutkimustuotos: OpinnäyteVäitöskirjaArtikkelikokoelma

    TY - THES

    T1 - Insights into particle formation and analysis

    AU - Pessi, Jenni Johanna

    PY - 2017/11/3

    Y1 - 2017/11/3

    N2 - This thesis consists of two parts, particle formation and analysis. In the first part, particle formation in microfluidic devices and in devices employing supercritical fluids is investigated, and in the second part, essential issues in analytical methods for determining drug release and solid-state properties are addressed. Microfluidic technology was employed to produce microcapsules for protein formulations. The microcapsules were produced with a biphasic flow to create water-oil-water double emulsion droplets with ultrathin shells. All the particles were found to be intact and with a particle size of 23 - 47 µm. The encapsulation efficiency of bovine serum albumin in the microcapsules was 84%. This study demonstrates that microfluidics is a powerful technique for engineering formulations for therapeutic proteins. A new, robust, stable, and reproducible method based on expansion of supercritical solutions using carbon dioxide as a solvent was developed to produce nanoparticles. The method, Controlled Expansion of Supercritical Solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Controlled pressure reduction keeps the particle growth and production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm). The Lyophilic Matrix (LM) method was developed for investigating dissolution rates of nanoparticles, powders, and particulate systems. The LM method is based on its ability to discriminate between non-dissolved particles and the dissolved species. In the LM method, the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while inhibiting dispersion of non-dissolved particles without presenting a substantial diffusion barrier. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. Time-gated Raman spectroscopy was applied for solid-state analysis of fluorescent powder mixtures. A setup with a 128 × (2) × 4 CMOS SPAD detector was used for the quantitative analysis of solid-state forms of piroxicam. Time-gating provides an instrumental method for rejecting the fluorescence signal. This study demonstrated that traditional PLS analysis of time-gated Raman spectra resulted in mean RMSE of 4.1%. The time-gated Raman spectroscopy method shows potential for relatively routine quantitative solid-state analysis of photoluminescent pharmaceuticals.

    AB - This thesis consists of two parts, particle formation and analysis. In the first part, particle formation in microfluidic devices and in devices employing supercritical fluids is investigated, and in the second part, essential issues in analytical methods for determining drug release and solid-state properties are addressed. Microfluidic technology was employed to produce microcapsules for protein formulations. The microcapsules were produced with a biphasic flow to create water-oil-water double emulsion droplets with ultrathin shells. All the particles were found to be intact and with a particle size of 23 - 47 µm. The encapsulation efficiency of bovine serum albumin in the microcapsules was 84%. This study demonstrates that microfluidics is a powerful technique for engineering formulations for therapeutic proteins. A new, robust, stable, and reproducible method based on expansion of supercritical solutions using carbon dioxide as a solvent was developed to produce nanoparticles. The method, Controlled Expansion of Supercritical Solution (CESS), uses controlled mass transfer, flow, pressure reduction, and particle collection in dry ice. CESS offers control over the crystallization process as the pressure in the system is reduced according to a specific profile. Controlled pressure reduction keeps the particle growth and production process stable. With CESS, we produced piroxicam nanoparticles, 60 mg/h, featuring narrow size distribution (176 ± 53 nm). The Lyophilic Matrix (LM) method was developed for investigating dissolution rates of nanoparticles, powders, and particulate systems. The LM method is based on its ability to discriminate between non-dissolved particles and the dissolved species. In the LM method, the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while inhibiting dispersion of non-dissolved particles without presenting a substantial diffusion barrier. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. Time-gated Raman spectroscopy was applied for solid-state analysis of fluorescent powder mixtures. A setup with a 128 × (2) × 4 CMOS SPAD detector was used for the quantitative analysis of solid-state forms of piroxicam. Time-gating provides an instrumental method for rejecting the fluorescence signal. This study demonstrated that traditional PLS analysis of time-gated Raman spectra resulted in mean RMSE of 4.1%. The time-gated Raman spectroscopy method shows potential for relatively routine quantitative solid-state analysis of photoluminescent pharmaceuticals.

    KW - 317 Pharmacy

    M3 - Doctoral Thesis

    SN - 978-951-51-3679-4

    T3 - Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis

    PB - University of Helsinki

    CY - Helsinki

    ER -

    Pessi JJ. Insights into particle formation and analysis. Helsinki: University of Helsinki, 2017. 112 s. (Dissertationes Scholae Doctoralis Ad Sanitatem Investigandam Universitatis Helsinkiensis; 52/2017).