title: Analysis of thin baked-on silicone layers by FTIR and 3D-Laser Scanning Microscopy.
abstract: 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.
authors: Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstr. 5, 81377 München, Germany.
authors: Stefanie
authors: S
authors: Funke
authors: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors: Julia
authors: J
authors: Matilainen
authors: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors: Heiko
authors: H
authors: Nalenz
authors: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors: Karoline
authors: K
authors: Bechtold-Peters
authors: F. Hoffmann-La Roche Ltd, Pharmaceutical Development & Supplies, PTD Biologics Europe (PTDE-P), 4070 Basel, Switzerland.
authors: Hanns-Christian
authors: HC
authors: Mahler
authors: Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstr. 5, 81377 München, Germany. Electronic address: Wolfgang.Friess@lrz.uni-muenchen.de.
authors: Wolfgang
authors: W
authors: Friess
mesh_terms: D055598:Chemical Phenomena; D004655:Emulsions; D006536:Heptanes / Q000737:chemistry; D006358:Hot Temperature; D021621:Imaging, Three-Dimensional; D007277:Injections, Jet / Q000295:instrumentation*; D057230:Limit of Detection; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D009330:Nebulizers and Vaporizers; D010865:Pilot Projects; D012827:Silicone Oils / Q000737:chemistry*; D012828:Silicones / Q000032:analysis* / Q000737:chemistry / Q000302:isolation & purification; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013594:Syringes
chemical_list: D004655:Emulsions; D006536:Heptanes; D012827:Silicone Oils; D012828:Silicones; D012997:Solvents; C028618:n-heptane
keywords: 3D-Laser Scanning Microscopy; Cartridge; FTIR; Silicone distribution; Silicone layer thickness; Siliconization