Funke Stefanie, Matilainen Julia, Nalenz Heiko, Bechtold-Peters Karoline, Mahler Hanns-Christian, Friess Wolfgang
Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstr. 5, 81377 München, Germany.
F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
Eur J Pharm Biopharm. 2015 Oct;96:304-13. doi: 10.1016/j.ejpb.2015.08.009. Epub 2015 Aug 24.
Pre-filled syringes (PFS) and auto-injection devices with cartridges are increasingly used for parenteral administration. To assure functionality, silicone oil is applied to the inner surface of the glass barrel. Silicone oil migration into the product can be minimized by applying a thin but sufficient layer of silicone oil emulsion followed by thermal bake-on versus spraying-on silicone oil. Silicone layers thicker than 100nm resulting from regular spray-on siliconization can be characterized using interferometric profilometers. However, the analysis of thin silicone layers generated by bake-on siliconization is more challenging. In this paper, we have evaluated Fourier transform infrared (FTIR) spectroscopy after solvent extraction and a new 3D-Laser Scanning Microscopy (3D-LSM) to overcome this challenge. A multi-step solvent extraction and subsequent FTIR spectroscopy enabled to quantify baked-on silicone levels as low as 21-325μg per 5mL cartridge. 3D-LSM was successfully established to visualize and measure baked-on silicone layers as thin as 10nm. 3D-LSM was additionally used to analyze the silicone oil distribution within cartridges at such low levels. Both methods provided new, highly valuable insights to characterize the siliconization after processing, in order to achieve functionality.
预充式注射器（PFS）和带药筒的自动注射装置越来越多地用于肠胃外给药。为确保功能正常，硅油被涂覆在玻璃药筒的内表面。通过涂覆一层薄而足够的硅油乳液，然后进行热烘烤而非喷涂硅油，可以将硅油向产品中的迁移降至最低。由常规喷涂硅化产生的厚度超过100nm的硅氧烷层可以使用干涉轮廓仪进行表征。然而，对通过烘烤硅化产生的薄硅氧烷层进行分析更具挑战性。在本文中，我们评估了溶剂萃取后的傅里叶变换红外（FTIR）光谱和一种新型的三维激光扫描显微镜（3D-LSM），以克服这一挑战。多步溶剂萃取及随后的FTIR光谱能够量化每5mL药筒中低至21 - 325μg的烘烤硅油含量。成功建立了3D-LSM，以可视化和测量薄至10nm的烘烤硅氧烷层。此外，3D-LSM还用于分析如此低含量下药筒内硅油的分布情况。这两种方法为表征加工后的硅化情况提供了全新的、极具价值的见解，以便实现其功能。
