(M1130-07-38) An Assessment of Factors Influencing the Integrity of Sprayed-On Silicone Oil Layer in Prefilled Syringes and Functionality of Prefilled Syringes

Purpose: There is a continuous growth in the prefilled syringe (PFS) market for subcutaneous delivery of biologics. The inner wall of PFS is coated with silicone oil using a standard sprayed-on method to decrease surface friction for smooth plunger movement during drug administration. The biologics or biologics formulation components (buffer, surfactant, and stabilizers) can interact with the sprayed-on silicone oil layer over the target shelf life of drug product resulting in a modification of the silicone oil coating (i.e., change in surface hydrophobicity). Changes in the silicone oil coating can have a negative impact on the functionality of PFS (i.e., increased glide force and delivery time)^1-3. This study assesses the impact of 2 buffers, PS80, stabilizers, and 2 proteins (mAb1 and mAb2) on the modification of the sprayed-on silicone oil coating and functional performance of PFSs.

Methods: Siliconized (sprayed-on) syringes with minor differences in glass manufacturing process (SpSi 1 and SpSi 2) were filled with a total of 9 solutions (S1 to S9) containing either citrate or histidine buffer in the presence or absence of PS80, stabilizers, and 2 proteins (mAb 1 or mAb 2) at 100 mg/mL concentration.  Syringes with a cross-linked (CL) silicone oil coating were used as a study control. All syringes were placed on stability at 30°C and 40 °C for up to 3 months. Samples were tested for changes in the surface hydrophobicity of the silicone oil layer by water contact angle (WCA), the presence of silicone oil subvisible particles (SVPs) by Micro flow imaging (MFI), the amount of silicone oil in drug product solution and on the syringe barrel by inductively coupled plasma optical emission spectroscopy (ICP-OES), the silicone oil coverage by FlexHD, and the functionality of syringes by glide force.

Results: Water contact angle data are presented in Figure 1. After 3 months of storage at 30°C and 1 month at 40°C, SpSi 1 syringes showed no noticeable changes in WCA for citrate-based samples without protein (S1-S3) and minor decreases in WCA for citrate-based samples with mAb1 (S4); SpSi 1 syringes showed decreases in WCA for all histidine-based samples with PS80 (S6-S9); SpSi 2 syringes showed no noticeable changes in WCA for all citrate-based samples; but decreases in WCA for histidine-based samples that contained either mAb1 or mAb2. A decrease in WCA was also observed in CL syringes filled with the histidine-based mAb 1 formulation (S8). Overall, SpSi 2 syringes maintained hydrophobicity better than SpSi 1 syringes, and histidine buffer formulations containing PS80 (S6-S9) reduced hydrophobicity more than citrate buffer formulations containing PS80 (S2-S4) in SpSi 1 and SpSi 2 syringes. MFI (silicone oil SVP counts ≥5 µm) and ICP-OES data are presented in Figure 2. At initial and after 3 months of storage at 30°C and 1 month at 40°C, silicone oil SVP counts ≥5 µm were generally higher in PS80-containing solutions compared to buffer-only solutions across syringe types. SpSi 2 and CL syringes generally had lower particle counts than SpSi 1 syringes across solution types after storage at 30°C for 3 months and 40°C for 1 month. ICP-OES data showed that silicone oil content in the sample solutions after 3 months at 30°C remained highly similar regardless of solution or syringe type. This indicates that there is no direct relationship between the amount of free silicone oil present in the sample solution and the silicone oil SVP counts. By FlexHD silicone oil coverage in SpSi 1 and SpSi 2 syringes were comparable. The glide force results (Figure 3) indicate that there is minimal impact of formulation components (i.e., buffers, PS80, stabilizers) or syringe type (SpSi 1 or SpSi 2, CL) on the glide force. The viscosity of buffer solutions ranged from 1.0-1.3cP and the viscosity of protein solutions in histidine formulations ranged from 3.7-3.8cP (shown in Figure 3). An increase in glide force was observed for solutions containing protein, which is attributed to increased viscosity of these formulations.

Conclusion: Based on the above data, it can be concluded that SpSi 2 syringes showed minimal changes in the hydrophobicity of the silicone oil layer and silicone oil SVP counts when compared to SpSi 1 syringes. Results for CL syringes were generally comparable to SpSi 2 syringes across assays. The performance of citrate-based formulations was better than histidine-based formulations by WCA and MFI. Formulations containing PS80 showed increased susceptibility to reductions in WCA, and formulations containing protein showed the highest susceptibility to reductions in WCA. Formulations containing PS80 showed increased silicone oil SVP counts. Overall, this study showed that the integrity of the silicone oil layer is impacted by multiple factors including glass manufacturing process, siliconization method, and formulation components such as buffer system, PS80 and protein, but glide force was largely affected by the viscosity of product solutions.

References: 1. Shi et al. Impact of Drug Formulation Variables on Silicone Oil Structure and Functionality of Prefilled Syringe System. PDA J Pharm Sci Technol. (2018)
2. Fang et al. Drug Formulation Impact on Prefilled Syringe Functionality and Autoinjector Performance. PDA J Pharm Sci Technol. (2020).
3. Fang et al. Physicochemical Excipient-Container Interactions in Prefilled Syringes and Their Impact on Syringe Functionality. PDA J Pharm Sci Technol. (2021).

Acknowledgements: We would like to acknowledge Himanshu Sharma, Jim Ludlow and Andreas Sophocleous from GSK for their support and guidance on this work.

Figure 1. Water Contact Angle Data

Figure 2.) MFI and ICP-OES Data

Figure 3.) Glide Force and Viscosity Data