Physicochemical Excipient-Container Interactions in Prefilled Syringes and Their Impact on Syringe Functionality.

Previous studies have shown that parenteral formulation excipients can interact with the silicone oil in prefilled syringes, thereby causing variations in glide force that affect the performance of autoinjectors. Thus, it is crucial to control the glide force of the prefilled syringes to mitigate the potential risk of dose inaccuracies. This study provided a systematic understanding of the chemical interactions between the excipients, physical interactions between the excipients and the container, as well as their impact on the functional performance of prefilled syringes. The design of experiment approach used in this study generated statistically meaningful data, which confirmed that different excipients caused varying increase in glide force in siliconized prefilled syringes. The data indicated that poloxamer 188 can more effectively maintain stable glide forces during accelerated storage conditions compared with polysorbate 80. This finding was further enhanced using Hansen solubility parameters theory, which provided a fundamental understanding of the mechanisms behind the physical interactions. Chemical stability analysis of the surfactants suggested that degradation of excipients also impacts syringe functionality. In summary, the results revealed the unique interactions between parenteral pharmaceutical excipients and primary packaging systems and the physicochemical foundation behind them.

Drug Formulation Impact on Prefilled Syringe Functionality and Autoinjector Performance.

Given the surging interest in developing prefilled syringe and autoinjector combination products, investment in an early compatibility assessment is critical to prevent unwarranted drug/container closure interactions and avoid potential reformulation during late stages of drug development. In addition to the standard evaluation of drug stability, it is important to consider container closure functionality and overall device performance changes over time because of drug-container closure component interaction. This study elucidated the mechanisms that cause changes in syringe glide force over time and the impact on the injection duration. It was an expansion of the previous work, which indicated that drug formulation variables such as formulation excipients and pH affect syringe functionality over time. The current study described an investigative process for troubleshooting prolonged and variable autoinjector injection time caused by an increased syringe glide force variability over time. This increase in glide force variability stems from two root causes, namely plunger dimensional variation and syringe silicone oil change over time. The results demonstrated (a) the underlying factors of silicone oil change in the presence of drug formulation matrices, (b) accelerated stability of syringe glide force as a good indicator of long-term, real-time stability, and (c) that buffer matrix-filled syringes can be used to predict the syringe functionality and stability of drug product-filled syringes. Based on the experimental findings of a variety of orthogonal characterization techniques including contact angle, interfacial tension, and calculation of Hansen solubility parameters, it is proposed that silicone oil change is caused by formulation excipients and a complex set of phenomena summarized as "wet, wash, and delube" processes.

Modeling the Permeation Rates of Organic Migrants through a Fluoropolymer Film.

Polymer films have been widely used as barriers for blocking certain organic molecules (such as leachables and extractables) in both food and parenteral pharmaceutical packaging applications. However, a good understanding of the barrier properties of those polymer films is still lacking for combination drug product manufacturers to make practical risk-based assessments regarding the effectiveness of the barrier films against potential leachables. The present work addressed this issue by a combined theoretical/experimental approach-a new mathematical model based on Hansen Solubility Parameters, the size and shape of organic molecules, was developed to quantitatively estimate the Steady-State Permeation Rate of organic migrants through a model ethylene-tetrafluoroethylene fluoropolymer film by considering contributions from both solubility and diffusivity. This model facilitates expedited screening of potential leachables, allowing for experimental focus on higher-risk leachables and ultimately enabling rapid combination drug product development.LAY ABSTRACT: Currently, there is a shortage of simple mathematical models that can accurately estimate the effectiveness of the barrier properties of polymer films; therefore, practical assessment of the barrier properties of these materials is mainly realized by experimental measurements of the permeation rates of interested migrants. These measurements can be time-consuming, costly, and inaccurate. Sometimes these measurements are even impossible if the migrant molecules are not commercially available (although we might know their molecular structures). Thus, there is a need for a practical and easy-to-use mathematical model that can estimate/predict the permeation rate through these barrier materials. To satisfy this need, we developed a new model based on the molecular polarity, size, and shape of migrant molecules to quantitatively estimate the permeation rate of the migrant molecules through these barrier materials. This model will be useful for applications in both food and drug packaging. Additionally, this model will be useful for medical devices or containers that will hold or store organic drug molecules, such as medical tubing or IV bags. Finally, organic compounds used in inks and adhesives that will permeate through packaging materials could also be modeled in the same fashion.

Model Protein Adsorption on Polymers Explained by Hansen Solubility Parameters.

Hansen solubility parameters (HSP) theory has been successful in explaining the wettability of organic solvents on polymer surfaces and miscibility of different polymers. Here, we demonstrate that the amount of bovine serum albumin (BSA) protein adsorption on different polymer surfaces can also be explained by HSP. Interestingly, the HSP of the adsorbed BSA proteins calculated from the protein adsorption data is different than the HSP of native BSA protein itself. The HSP of the adsorbed BSA proteins are more hydrophobic than the native BSA protein. This observation suggested adsorbed BSA proteins are partially denatured and exposed their hydrophobic core toward the polymer surfaces. These results highlight a new strategic direction to understand interaction of protein with a surface: a theoretical approach that compliments experimental approach. The model in this study could be used to predict the amount of BSA adsorption on a polymer or any other solid surface, if the HSP of that surface is known. Further, the model can serve as a prescreen method to identify surfaces that are problematic at the outset and inform subsequent empirical studies to select packaging that will have the least adsorption for the specific biologic application.