Control over particle size distribution by autoclaving poloxamer-stabilized trimyristin nanodispersions

Katrin Göke, Elin Roese, Andreas Arnold, Judith Kuntsche, Heike Bunjes*

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field-flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones.

OriginalsprogEngelsk
TidsskriftMolecular Pharmaceutics
Vol/bind13
Udgave nummer9
Sider (fra-til)3187-3195
ISSN1543-8384
DOI
StatusUdgivet - 2016

Fingeraftryk

Poloxamer
Particle Size
Lipids
Field Flow Fractionation
Pharmaceutical Preparations
Scanning Transmission Electron Microscopy

Citer dette

Göke, Katrin ; Roese, Elin ; Arnold, Andreas ; Kuntsche, Judith ; Bunjes, Heike. / Control over particle size distribution by autoclaving poloxamer-stabilized trimyristin nanodispersions. I: Molecular Pharmaceutics. 2016 ; Bind 13, Nr. 9. s. 3187-3195.
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abstract = "Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field-flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones.",
keywords = "asymmetrical flow field-flow fractionation (A4F), autoclaving, differential scanning calorimetry, laser diffraction, lipid nanoparticles, particle size distribution, photon correlation spectroscopy",
author = "Katrin G{\"o}ke and Elin Roese and Andreas Arnold and Judith Kuntsche and Heike Bunjes",
year = "2016",
doi = "10.1021/acs.molpharmaceut.6b00395",
language = "English",
volume = "13",
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Control over particle size distribution by autoclaving poloxamer-stabilized trimyristin nanodispersions. / Göke, Katrin; Roese, Elin; Arnold, Andreas; Kuntsche, Judith; Bunjes, Heike.

I: Molecular Pharmaceutics, Bind 13, Nr. 9, 2016, s. 3187-3195.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Control over particle size distribution by autoclaving poloxamer-stabilized trimyristin nanodispersions

AU - Göke, Katrin

AU - Roese, Elin

AU - Arnold, Andreas

AU - Kuntsche, Judith

AU - Bunjes, Heike

PY - 2016

Y1 - 2016

N2 - Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field-flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones.

AB - Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field-flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones.

KW - asymmetrical flow field-flow fractionation (A4F)

KW - autoclaving

KW - differential scanning calorimetry

KW - laser diffraction

KW - lipid nanoparticles

KW - particle size distribution

KW - photon correlation spectroscopy

U2 - 10.1021/acs.molpharmaceut.6b00395

DO - 10.1021/acs.molpharmaceut.6b00395

M3 - Journal article

VL - 13

SP - 3187

EP - 3195

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 9

ER -