Development of a synthetic human lung fluid simulant for applications in inhalation biopharmaceutics

Development of a synthetic human lung fluid simulant for applications in inhalation biopharmaceutics

Mireille Hassoun1, Paul G. Royall1, Richard D. Harvey2, Mark Parry3, Ben Forbes1

1Institute of Pharmaceutical Science, King’s College London, SE1 9NH, UK

2Institute of Pharmacy, Martin-Luther-Universitat Halle-Wittenberg, 06108 Halle (Saale), Germany

3Intertek-Melbourn Scientific Limited, Saxon Way, Melbourn, SG8 6DN, UK

Summary

The purpose of this study was to characterise a simulated lung lining fluid (SLF) and develop a quality specification for the simulant, which has applications in inhalation biopharmaceutics research. Changes in pH, viscosity, conductivity, surface tension and osmolality were used to assess the stability of SLF when stored at 4, 20 and 37°C for 0, 7, 14 and 28 days. The results supported the hypothesis that thermal degradation (e.g. hydrolysis and lipid perioxidation) occurs at higher temperatures over this time period and can be detected by a change in these parameters. From day 7, the pH of SLF was significantly lower at 20 and 37°C compared to SLF stored at 4°C (one-way ANOVA, p ≤ 0.05). The viscosity also decreased at the higher temperatures progressively over time. The surface tension reduced, from 54.9 ± 0.4 mN/m for SLF stored at 4°C to 53.5 ± 0.5 and 53.8 ± 0.2 mN/m for SLF stored at 20 and 37°C, respectively. Osmolality was higher at all time points for the SLF stored at 20 and 37°C compared to SLF stored at 4°C; at day 7 osmolality was 1096.8 ± 10.8, 1193.6 ± 26.9 and 1331.5 ± 8.2 mOsmol/Kg for SLF stored at 4, 20 and 37°C, respectively. The change in osmolality was attributed to evaporation of water from HBSS causing an increase in ion concentration.  In conclusion, a quality specification for SLF was developed and showed that SLF stored at 4°C was stable for 14 days.

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