The impact of solvent selection

TY - JOUR

T1 - The impact of solvent selection

T2 - strategies to guide the manufacturing of liposomes using microfluidics

AU - Webb, Cameron

AU - Khadke, Swapnil

AU - Schmidt, Signe Tandrup

AU - Roces, Carla B.

AU - Forbes, Neil

AU - Berrie, Gillian

AU - Perrie, Yvonne

PY - 2019/12/4

Y1 - 2019/12/4

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.

KW - liposomes

KW - microfluidics

KW - solvents

KW - formulation

KW - particle size

KW - PEGylation

KW - alcohol

UR - https://www.mdpi.com/journal/pharmaceutics

U2 - 10.3390/pharmaceutics11120653

DO - 10.3390/pharmaceutics11120653

M3 - Article

VL - 11

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 12

M1 - 653

ER -