Impact of dimensional variability of primary packaging materials on the break-loose and gliding forces of prefilled syringes.

ABSTRACT

A prefilled syringe (PFS) should be able to be adequately and consistently extruded during injection for optimal safe drug delivery and accurate dosing. To facilitate appropriate break-loose and gliding forces (BLGF) required during injection, certain primary packaging materials (PPM) such as the syringe barrel and plunger are usually coated with silicone oil, which acts as a lubricant. Due to its direct contact with drug, silicone oil can increase the number of particles in the syringe, which could lead to adverse interactions. Compliance with regulatory defined silicone oil quantities in certain drug products, such as ophthalmic, presents a trade-off with the necessity for desirable low and consistent BLGF. In addition to its siliconization, the dimensional accuracy of PPM has an important role in controlling BLGF. The dimensions of PPM are individualized depending on the product and its design and have certain tolerances that must be met during manufacturing. Most studies on ophthalmic focused on the adverse interactions between silicone oil and the drug. To the authors' knowledge, there have been no public studies so far that have investigated the impact of the dimensional variability of PPM on the BLGF in ophthalmic PFS. In this study, we applied advanced optical shaft and tactile measuring technologies to investigate this impact. The syringes investigated, were first sampled during aseptic production, and tested for BLGF. Subsequently, defined dimensions of PPM were measured individually. The results showed that the dimensional variability of PPM can have a negative impact on the BLGF, despite their conformity to specifications, which indicates that the currently available market quality of PPM is improvable for critical drug products such as ophthalmic. This study could serve as an approach to define product-specific requirements for primary packaging combinations and thus appropriate specifications based on data during the development stage of drug products.