Interaction of preservatives with contact materials during filling and storage of parenteral liquid formulations

Abstract

Silicone tubing is a frequently used material in pharmaceutical filling processes for parenteral formulations, as its characteristics like flexibility, chemical resistance and easy handling make it particularly suitable for these purposes. This study investigated the time-dependent interaction of phenol and m-cresol with silicone tubing and other broadly applied contact materials used during the filling and transport processes of parenteral formulations. Phenol losses could be observed after incubation in silicone tubing, depending on the inner diameter (ID). This has been demonstrated for process interruptions of up to 120 min. A loss of 40 % could be observed for a small ID of 3.2 mm which can be found close to filling needles, and up to 12 % for larger tubes with an ID of 9.5 mm commonly used for sterile filtration and transport processes. Analysis of tubes with varying ID revealed a linear relationship between the decrease of phenol and the surface-to-volume ratio. m-cresol showed an even more pronounced loss in silicone tubing. Fluorinated polymers and thermoplastic elastomers were also analyzed, and no loss of phenol and m-cresol was observed. Pumping tests revealed that shear forces in peristaltic pumps led to strong particle formation in selected tubing. A strong increase in particle concentration was observed in thermoplastic elastomers, particularly in PharMed® BPT tubing. In contrast, the C-Flex® tubing demonstrated minimal particle formation. Fluorinated polymers are not compatible with peristaltic pumps, which is why they were not analyzed regarding pumpability. Although silicone tubes are not impervious to preservatives such as phenol, they did not generate particles when pumped.