Dissolution of man-made vitreous fibres (MMVF) using the USP-4: Part I. Fluid choice for closed-loop configuration tests

In this research, we extended our examination of the US pharmacopeia apparatus 4 (USP-4) application for the development of an in vitro acellular dissolution protocol for man-made vitreous fibres (MMVF¹). The aim of this study was to achieve robust differentiation in solubility of glass and stone wool fibres using a USP-4 closed-loop configuration. For this, synthetic lung fluids representing extra-cellular conditions of the lungs (pH 7.4) and the environment in the phagolysosome (pH 4.5) were evaluated and tested in closed-loop dissolution experiments with multiple fibres across several labs. Our results showed that it was possible to differentiate between high- and low-solubility fibres using all candidate fluids. However, we found that it was crucial to limit the pH variability and to adapt the levels of organics in the fluid, as they impacted the dissolution of the fibres. Our findings indicated good inter-lab variability of an in vitro acellular biosolubility testing with the USP-4. For further development of the USP-4 closed loop configuration protocol, we propose focusing on phosphate-based buffers for pH 7.4 and acetate buffers or PSF + 10 mg/L citrate for pH 4.5.