Combination drug products, based on therapeutic proteins, are gaining popularity due to easy administration from the patient perspective. Designing and developing a combination drug product is a very complex process, and most early efforts were spent typically on the stability of the drug substance. The drug/packaging compatibility tends to be over-looked in the early stage of the development of a combination drug product, an issue which could cause serious future problems such as a device malfunction or a drug safety issue. Glass-based pre-filled syringes (PFS) are the most commonly used PFS in many combination drug products. Silicone oil is commonly used as a lubricant in the glass PFS to control break-loose and extrusion forces. However, the stability of the sprayed silicone oil layer can be altered by drug excipients, which then will have a profound effect on the break-loose and extrusion forces. We discovered that syringe friction change is caused by dynamic interactions of formulation excipients (surfactants, tonicity agents, buffering agents, etc.) with silicone oil, water, and glass. Our data shows that different excipients affect extrusion forces differently, and that those differences can be explained/predicted by Hansen Solubility Parameters theory. Compared to glass PFS, cyclic olefin polymer (COP) PFS showed more consistent and predictable extrusion forces. This can be explained/predicted by Hansen Solubility Parameters theory as well. Furthermore, COP PFS also showed significantly less variance in extrusion force within each injection, which is critical for certain applications such as autoinjectors. Therefore, we demonstrated how to choose the right excipients and their compatible primary packaging materials to perform their chemical functionality, without jeopardizing the combination drug product’s physical functionality and device performance. This process that takes drug/packaging compatibility into consideration at the early stage of designing and developing of a combination drug product will give drug manufacturers a tremendous advantage.

Understanding the excipient's effects on functionality of glass and polymer pre-filled syringes

2019 Fall National Meeting

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