Heavy Metal Contamination by the Use of Nanoporous Nickel-Based Membranes in Premix Membrane Emulsification: Implications for Product Purity

The production of lipid nanoemulsions can be achieved by premix membrane emulsification. The use of membranes made from the Ni-based superalloy CMSX-4 featuring a unique tortuous nanopore structure led to promising emulsification results in the past. To further qualify these membranes for a potential application in the pharmaceutical field, the risk of generating heavy metal contamination in the product due to leaching from the membranes during emulsification was investigated in this study. Regardless of membrane manufacturing parameters, heavy metal leaching was very similar for all CMSX-4-based membranes under investigation. An almost linear increase of heavy metal concentration with progressing membrane extrusion cycles hinted to ionic contaminations as the main cause for impurities in the processed liquid. An elevation in hydrodynamic stress applied to the system in the form of increased extrusion pressure or due to the extrusion of an emulsion resulted in higher heavy metal leaching rates. Still, concentrations in all final products did not exceed the limit values for Ni (<2 ppm), Co (<0.5 ppm), and Cr (<110 ppm) according to the ICH-Q3D(R2) guideline. A rinsing process applied before the actual use of the membranes contributed significantly to cleaning of the membrane.