Variability in Syringe Components and its Impact on Functionality of Delivery Systems

Abstract

Use of prefilled syringes (syringes prefilled with active drug) is becoming increasingly common for injectable drugs. Compared to vials, prefilled syringes offer higher dose accuracy and ease of use due to fewer steps required for dosage. Convenience to end users can be further enhanced through the use of prefilled syringes in combination with delivery devices such as autoinjectors. These devices allow patients to self-administer the drug by following simple steps such as pressing a button. These autoinjectors are often spring-loaded and are designed to keep the needle tip shielded prior to injection. Because the needle is not visible to the user, such autoinjectors are perceived to be less invasive than syringes and help the patient overcome the hesitation associated with self-administration. In order to successfully develop and market such delivery devices, we need to perform an in-depth analysis of the components that come into play during the activation of the device and dose delivery. Typically, an autoinjector is activated by the press of a button that releases a compressed spring; the spring relaxes and provides the driving force to push the drug out of the syringe and into the site of administration. Complete understanding of the spring force, syringe barrel dimensions, needle size, and drug product properties is essential for robust device design. It is equally important to estimate the extent of variability that exists in these components and the resulting impact it could have on the performance of the device. In this work, we studied the impact of variability in syringe and device components on the delivery forces associated with syringe injection. More specifically, the effect of barrel size, needle size, autoinjector spring force, and frictional forces has been evaluated. An analytical model based on underlying physics is developed that can be used to predict the functionality of the autoinjector.

Characterization of protein rheology and delivery forces for combination products

“…Three specific aspects of the protein–device combination product are explored in this study: (a) the characterization of product viscosity over a broad concentration and temperature range, (b) the characterization of product–syringe interactions and its impact on friction forces associated with delivery, and (c) the characterization of product rheological behavior under the high shear rates (∼100,000 s −1 ) associated with syringe injection. The effect of component variability on the delivery forces and injection time has been studied earlier and the results have been presented in a separate article 4…”

Quality by Design for Biopharmaceutical Drug Product Development

“…Upon the improvement of the siliconization process (deemed a CPP) by the syringe supplier, the silicone oil distribution within PFS, and consequent auto-injector performance were improved (Hwang 2008). In a 2011 PDA publication, it was reported that needle ID variation impacted injection force and time, as expected (Rathore et al 2011). However, it is the authors' understanding that, in general, the industry lacks a generally applied CS in silicone oil distribution and needle ID.…”

“…Therefore, most auto-injectors have to be "custommade" for the specific PFS product of interest even if many detailed "considerations" can be leveraged from one design to the other. A detailed description on the proper characterization of PFS can be found in several publications (Rathore et al 2011). Briefly, one must have access to representative ranges of properties of the PFS components and use them to guide the design and testing of the auto-injector.…”

Calculation of injection forces for highly concentrated protein solutions

“…Equation 3 Rathore et al reported Equations 1 to 3 to express the injection force for shear thinning fluids (Rathore et al, 2012;Rathore et al, 2011). In a recent study, Allmendinger et al employed a slightly different approach, where they did not use the shear rate at the wall, but used an average shear rate, which takes into consideration the non-linear shear rate changes throughout the needle diameter, thus coming up with the "effective shear rate" (Allmendinger et al, 2014) :…”