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 (MMVF 1 1 Man-made vitreous fibres (MMVF) is the terminology commonly used in the European Union to refer to mineral wool fibres, it is also the terminology used in the classification entries for these materials in Regulation (EC) No 1272/2008 classification, labelling and packaging of substances and mixtures as the term synthetic vitreous fibres (SVF) is also used in literature and other jurisdictions to refer to mineral wool fibres. ). 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. • USP-4 closed loop was used to obtain MMVF dissolution in vitro test endpoint • Simplified lung fluids were selected for USP-4 closed loop MMVF dissolution • Clear fibre-fibre differentiation and good lab-lab reproducibility was observed • Phosphate and acetate buffers or PSF + 10 mg/L citrate are suggested • Further USP-4 open loop tests of MMVF will follow to access dissolution kinetics
Okhrimenko et al. (Sun,) studied this question.