Design and development of a biorelevant simulated human lung fluid

Mireille Hassoun; Paul G. Royall; Richard D. Harvey; Ben Forbes

doi:10.1016/j.jddst.2018.08.006

Design and development of a biorelevant simulated human lung fluid

Mireille Hassoun, Paul G. Royall, Richard D. Harvey, Ben Forbes

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Abstract

Biorelevant fluids are required to enable meaningful in vitro experimental determinations of the biopharmaceutical properties of inhaled medicines, e.g. drug solubility, particle dissolution, cellular uptake. Our aim was to develop a biorelevant simulated lung fluid (SLF) with a well-defined composition and evidence-based directions for use. The SLF contained dipalmitoylphosphotidylcholine, dipalmitoylphosphatidylglycerol, cholesterol, albumin, IgG, transferrin and antioxidants. Freshly made SLF had pH 7.2, viscosity 1.138 × 10−3 Pa s, conductivity 14.5 mS/m, surface tension 54.9 mN/m and density 0.999 g/cm3. Colour, surface tension and conductivity were the most sensitive indicators of product deterioration. The simulant was stable for 24 h and 48 h at 37 °C and 21 °C, respectively, (in-use stability) and for 14 days when stored in a refrigerator (storage stability). To extend stability, the SLF was vacuum freeze-dried in batches to produce lyophilised powder that can be reconstituted readily when needed at the point of use. In conclusion, we have reported the composition and manufacture of a biorelevant, synthetic SLF, provided a detailed physico-chemical characterisation and recommendations for how to store and use a product that can be used to generate experimental data to provide inputs to computational models that predict drug bioavailability in the lungs.

Original language	English
Pages (from-to)	485-491
Journal	Journal of drug delivery science and technology
Volume	47
Early online date	9 Aug 2018
DOIs	https://doi.org/10.1016/j.jddst.2018.08.006
Publication status	Published - Oct 2018

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Design and development of_HASSOUN_Accepted8August2018_GOLD VoR (CC BY)Final published version, 1.24 MBLicence: CC BY

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title = "Design and development of a biorelevant simulated human lung fluid",

abstract = "Biorelevant fluids are required to enable meaningful in vitro experimental determinations of the biopharmaceutical properties of inhaled medicines, e.g. drug solubility, particle dissolution, cellular uptake. Our aim was to develop a biorelevant simulated lung fluid (SLF) with a well-defined composition and evidence-based directions for use. The SLF contained dipalmitoylphosphotidylcholine, dipalmitoylphosphatidylglycerol, cholesterol, albumin, IgG, transferrin and antioxidants. Freshly made SLF had pH 7.2, viscosity 1.138 × 10−3 Pa s, conductivity 14.5 mS/m, surface tension 54.9 mN/m and density 0.999 g/cm3. Colour, surface tension and conductivity were the most sensitive indicators of product deterioration. The simulant was stable for 24 h and 48 h at 37 °C and 21 °C, respectively, (in-use stability) and for 14 days when stored in a refrigerator (storage stability). To extend stability, the SLF was vacuum freeze-dried in batches to produce lyophilised powder that can be reconstituted readily when needed at the point of use. In conclusion, we have reported the composition and manufacture of a biorelevant, synthetic SLF, provided a detailed physico-chemical characterisation and recommendations for how to store and use a product that can be used to generate experimental data to provide inputs to computational models that predict drug bioavailability in the lungs.",

author = "Mireille Hassoun and Royall, {Paul G.} and Harvey, {Richard D.} and Ben Forbes",

year = "2018",

month = oct,

doi = "10.1016/j.jddst.2018.08.006",

language = "English",

volume = "47",

pages = "485--491",

journal = "Journal of drug delivery science and technology ",

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AU - Hassoun, Mireille

AU - Royall, Paul G.

AU - Harvey, Richard D.

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Y1 - 2018/10

N2 - Biorelevant fluids are required to enable meaningful in vitro experimental determinations of the biopharmaceutical properties of inhaled medicines, e.g. drug solubility, particle dissolution, cellular uptake. Our aim was to develop a biorelevant simulated lung fluid (SLF) with a well-defined composition and evidence-based directions for use. The SLF contained dipalmitoylphosphotidylcholine, dipalmitoylphosphatidylglycerol, cholesterol, albumin, IgG, transferrin and antioxidants. Freshly made SLF had pH 7.2, viscosity 1.138 × 10−3 Pa s, conductivity 14.5 mS/m, surface tension 54.9 mN/m and density 0.999 g/cm3. Colour, surface tension and conductivity were the most sensitive indicators of product deterioration. The simulant was stable for 24 h and 48 h at 37 °C and 21 °C, respectively, (in-use stability) and for 14 days when stored in a refrigerator (storage stability). To extend stability, the SLF was vacuum freeze-dried in batches to produce lyophilised powder that can be reconstituted readily when needed at the point of use. In conclusion, we have reported the composition and manufacture of a biorelevant, synthetic SLF, provided a detailed physico-chemical characterisation and recommendations for how to store and use a product that can be used to generate experimental data to provide inputs to computational models that predict drug bioavailability in the lungs.

AB - Biorelevant fluids are required to enable meaningful in vitro experimental determinations of the biopharmaceutical properties of inhaled medicines, e.g. drug solubility, particle dissolution, cellular uptake. Our aim was to develop a biorelevant simulated lung fluid (SLF) with a well-defined composition and evidence-based directions for use. The SLF contained dipalmitoylphosphotidylcholine, dipalmitoylphosphatidylglycerol, cholesterol, albumin, IgG, transferrin and antioxidants. Freshly made SLF had pH 7.2, viscosity 1.138 × 10−3 Pa s, conductivity 14.5 mS/m, surface tension 54.9 mN/m and density 0.999 g/cm3. Colour, surface tension and conductivity were the most sensitive indicators of product deterioration. The simulant was stable for 24 h and 48 h at 37 °C and 21 °C, respectively, (in-use stability) and for 14 days when stored in a refrigerator (storage stability). To extend stability, the SLF was vacuum freeze-dried in batches to produce lyophilised powder that can be reconstituted readily when needed at the point of use. In conclusion, we have reported the composition and manufacture of a biorelevant, synthetic SLF, provided a detailed physico-chemical characterisation and recommendations for how to store and use a product that can be used to generate experimental data to provide inputs to computational models that predict drug bioavailability in the lungs.

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DO - 10.1016/j.jddst.2018.08.006

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VL - 47

SP - 485

EP - 491

JO - Journal of drug delivery science and technology

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ER -

Design and development of a biorelevant simulated human lung fluid

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