TY - JOUR T1 - Methods to Determine the Silicone Oil Layer Thickness in Sprayed-On Siliconized Syringes JF - PDA Journal of Pharmaceutical Science and Technology JO - PDA J Pharm Sci Technol DO - 10.5731/pdajpst.2017.007997 SP - pdajpst.2017.007997 AU - Viviane Loosli AU - Oliver Germershaus AU - Henrik Steinberg AU - Sascha Dreher AU - Ulla Grauschopf AU - Stefanie Funke Y1 - 2018/01/01 UR - http://journal.pda.org/content/early/2018/01/16/pdajpst.2017.007997.abstract N2 - The silicone lubricant layer in prefilled syringes (PFS) has been investigated with regards to siliconization process performance, PFS functionality and drug product attributes such as subvisible particle levels in several studies in the past. However, adequate methods to characterize the silicone oil layer thickness and -distribution are limited and systematic evaluation is missing. In this study, white light interferometry (WLI) was evaluated to close this gap in method understanding. WLI demonstrated a good accuracy of 93-99 % for MgF2 coated, curved standards covering a thickness range of 115-473 nm. Thickness measurements for sprayed-on siliconized PFS with different representative silicone oil distribution patterns (homogeneous, pronounced siliconization at flange or needle-side, respectively) showed high instrument (0.5 %) and analyst precision (4.1 %). Different WLI instrument parameters (autofocus, protective shield, syringe barrel dimensions input, type of non-siliconized syringe used as base reference) had no significant impact on the measured average layer thickness (ALT). The obtained values from WLI applying a fully developed method (12 radial lines, 50 mm measurement distance, 50 measurements points) were in agreement with orthogonal results from combined white and laser interferometry and 3D-laser scanning microscopy. The investigated syringe batches (lot A and B) exhibited comparable longitudinal silicone oil layer thicknesses ranging from 170-190 nm to 90-100 nm from flange to tip and homogeneously distributed silicone layers over the syringe barrel circumference (110- 135 nm). Empty break loose (4-4.5 N) and gliding forces (2-2.5 N) were comparably low for both analyzed syringe lots. A silicone oil layer thickness of 100-200 nm was thus sufficient for adequate functionality in this particular study. Filling the syringe with a surrogate solution including short term exposure and emptying did not significantly influence the silicone oil layer at the investigated silicone level. It thus appears reasonable to use this approach to characterize silicone oil layers in filled syringes over time. The developed method characterizes non-destructively the layer thickness and distribution of silicone oil in empty syringes and provides fast access to reliable results. The gained information can be further used to support optimization of siliconization processes and increase the understanding of syringe functionality. ER -