The impact of solvent selection

strategies to guide the manufacturing of liposomes using microfluidics

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Abstract

The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposomes attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to IPA) increased the liposome particle size without impacting on liposome short-term stability or release charcteristics. Furthermore, solvent combinations such as methanol/IPA mixtures can be used to modify solvent polarity and the resultant liposome particle size. However, the impact of solvent choice on the liposome product is also influenced by the liposome formulation; liposomes containing charged lipids tended to show more sensitivity to solvent selection and formulations containing increased concentrations of cholesterol or PEG were less influenced by the choice of solvent. Indeed, incorporation of 14 wt % or more of pegylated lipid was shown to negate the impact of solvent selection.
Original languageEnglish
Article number653
Number of pages15
JournalPharmaceutics
Volume11
Issue number12
DOIs
Publication statusPublished - 4 Dec 2019

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Microfluidics
Liposomes
Methanol
Lipids
Particle Size
2-Propanol
Solubility
Ethanol
Cholesterol

Keywords

  • liposomes
  • microfluidics
  • solvents
  • formulation
  • particle size
  • PEGylation
  • alcohol

Cite this

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title = "The impact of solvent selection: strategies to guide the manufacturing of liposomes using microfluidics",
abstract = "The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposomes attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to IPA) increased the liposome particle size without impacting on liposome short-term stability or release charcteristics. Furthermore, solvent combinations such as methanol/IPA mixtures can be used to modify solvent polarity and the resultant liposome particle size. However, the impact of solvent choice on the liposome product is also influenced by the liposome formulation; liposomes containing charged lipids tended to show more sensitivity to solvent selection and formulations containing increased concentrations of cholesterol or PEG were less influenced by the choice of solvent. Indeed, incorporation of 14 wt {\%} or more of pegylated lipid was shown to negate the impact of solvent selection.",
keywords = "liposomes, microfluidics, solvents, formulation, particle size, PEGylation, alcohol",
author = "Cameron Webb and Swapnil Khadke and Schmidt, {Signe Tandrup} and Roces, {Carla B.} and Neil Forbes and Gillian Berrie and Yvonne Perrie",
year = "2019",
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language = "English",
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AU - Khadke, Swapnil

AU - Schmidt, Signe Tandrup

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AU - Forbes, Neil

AU - Berrie, Gillian

AU - Perrie, Yvonne

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N2 - The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposomes attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to IPA) increased the liposome particle size without impacting on liposome short-term stability or release charcteristics. Furthermore, solvent combinations such as methanol/IPA mixtures can be used to modify solvent polarity and the resultant liposome particle size. However, the impact of solvent choice on the liposome product is also influenced by the liposome formulation; liposomes containing charged lipids tended to show more sensitivity to solvent selection and formulations containing increased concentrations of cholesterol or PEG were less influenced by the choice of solvent. Indeed, incorporation of 14 wt % or more of pegylated lipid was shown to negate the impact of solvent selection.

AB - The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposomes attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to IPA) increased the liposome particle size without impacting on liposome short-term stability or release charcteristics. Furthermore, solvent combinations such as methanol/IPA mixtures can be used to modify solvent polarity and the resultant liposome particle size. However, the impact of solvent choice on the liposome product is also influenced by the liposome formulation; liposomes containing charged lipids tended to show more sensitivity to solvent selection and formulations containing increased concentrations of cholesterol or PEG were less influenced by the choice of solvent. Indeed, incorporation of 14 wt % or more of pegylated lipid was shown to negate the impact of solvent selection.

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KW - microfluidics

KW - solvents

KW - formulation

KW - particle size

KW - PEGylation

KW - alcohol

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