Design and development of a biorelevant simulated human lung fluid.
J Drug Deliv Sci Technol
; 47: 485-491, 2018 Oct.
Article
em En
| MEDLINE
| ID: mdl-30283501
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 1.138â¯×â¯10-3â¯Paâ¯s, conductivity 14.5â¯mS/m, surface tension 54.9â¯mN/m and density 0.999â¯g/cm3. Colour, surface tension and conductivity were the most sensitive indicators of product deterioration. The simulant was stable for 24â¯h and 48â¯hâ¯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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Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article