Comparison of the Extraction Properties of Binary Polysorbate 80/Water and Isopropanol/Water Solutions for Organic Substances Originating from a Parenteral Infusion Pump

Abstract

Pharmaceutical products come into contact with a diverse range of materials during their manufacture, storage, and administration. As a consequence of this contact, substances can leach from these materials and into the product, which may negatively affect its quality. It has been shown that leaching is increased for drug products that contain the nonionic surfactant polysorbate 80. However, the specific extraction properties of this surfactant are not well characterized. To address this deficiency in the knowledge base, the goal of this study was to determine the quantitative profile of 10 compounds extracted from a parenteral infusion pump by aqueous polysorbate 80 solutions. For comparison purposes, the extractable profiles of isopropanol/water solutions, which were utilized as a representative nonsurfactant solvent system, were also determined. The results obtained in this study have shown that relatively low (≤0.1%) concentrations of polysorbate 80 were capable of facilitating leaching, consistent with previous reports. More importantly, it was found that the full quantitative extractable profiles obtained for the polysorbate 80 solutions were not comparable to those obtained for isopropanol/water. However, when considering extractables as subsets based on their polarity, it was found that 10% and 45% isopropanol solutions could be used to simulate the quantitative profile of polysorbate 80 for polar and non-polar substances, respectively.

LAY ABSTRACT: When a pharmaceutical product comes into contact with a material during its manufacturing, packaging, or delivery, the substances present in that material may migrate (leach) into the product. Because these substances are not an intended constituent of the product, they have the potential to negatively impact its quality and ultimately patient safety. In general, the surfactant polysorbate 80 has been shown to facilitate the leaching of these substances when present in a product’s formulation; however, its specific extraction properties are not well understood. Thus, the goal of this study was to better characterize these properties by determining what compounds, and in what quantities, can be solubilized by polysorbate 80 solutions from a representative pharmaceutical packaging system. Additionally, a range of isopropanol/water solutions were also assessed as a comparative nonsurfactant solvent. The results obtained illustrate the differences between the extraction properties of polysorbate 80 and isopropanol/water, including the concentration of each required to extract substances and the overall quantitative profiles obtained. However, it was shown that isopropanol/water solutions could be used to simulate the extractable profiles obtained for a solution containing polysorbate 80 when evaluating compounds as subsets based on their physical properties, namely their solubility in an aqueous medium.