Preservative loss from silicone tubing during filling processes

详细信息    查看全文

• 作者：Verena Saller^a ; Julia Matilainen^b ; Christian Rothkopf^b ; Daniel Serafin^c ; Karoline Bechtold- Peters^b ; Hanns-Christian Mahler^b ; ¹ ; Wolfgang Friess^a ; ^{Wolfgang.Friess@lrz.uni-muenchen.de}
• 关键词：Silicone tubing ; Peristaltic pumping ; Filling processes ; Preservative ; Sorption ; Diffusion ; Permeability ; Fluoropolymer tubing
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2017
• 出版时间：March 2017
• 年：2017
• 卷：112
• 期：Complete
• 页码：109-118
• 全文大小：1699 K
• 卷排序：112

文摘

Significant loss of preservative was observed during filling of drug products during filling line stops. This study evaluated the losses of three commonly used preservatives in protein drugs, i.e. benzyl alcohol, phenol, and m-cresol. Concentration losses during static incubation were quantified and interpreted with regard to the potential driving forces for the underlying sorption, diffusion, and desorption steps. Partitioning from the solution into the silicone polymer was identified as the most decisive parameter for the extent of preservative loss. Additionally, the influence of tubing inner diameter, starting concentration as well as silicone tubing type was evaluated. Theoretical calculations assuming equilibrium between solution and tubing inner surface and one-directional diffusion following Fick’s first law were used to approximate experimental data. Since significant losses were found already after few minutes, adequate measures must be taken to avoid deviations during filling of preservative-containing protein solutions that may impact product quality or antimicrobial efficacy. As a possible alternative to the highly permeable silicone tubing, a specific make of fluoropolymer tubing was identified being suitable for peristaltic pumps and not showing any preservative losses.