Abstract

Subcutaneous injection by means of prefilled syringes allows patients to self-administrate high-concentration (100 g/L or more) protein-based drugs. Although the shear flow of concentrated globulins or monoclonal antibodies has been intensively studied and related to the injection force proper of SC processes, very small attention has been paid to the extensional behavior of this category of complex fluids. This work focuses on the flow of concentrated bovine serum albumin (BSA) solutions through a microfluidic “syringe-on-chip” contraction device which shares some similarities with the geometry of syringes used in SC self-injection. By comparing the velocity and pressure measurements in complex flow with rheometric shear measurements obtained by means of the “Rheo-chip” device, it is shown that the extensional viscosity plays an important role in the injection process of protinaceous drugs.Article HighlightsA microfluidic “syringe on chip” device mimicking the injection flow of protinaceous drugs has been developed.The velocity field of concentrated BSA solutions through the “syringe on chip” is Newtonian-like.The extensional viscosity of concentrated protein solutions should also be considered when computing injection forces through needles.

Highlights

  • Macromolecules such as monoclonal antibodies are increasingly being used for treating a large variety of diseases, including immunodeficiency, leukemia and arthritis [17], while globular proteins such as recombinant serum albumin are often employed as drug stabilizers [28, 59]

  • It must be observed that the flow of protein solutions through needles can be considered as a complex flow, because it contains a shear component, and a well-defined extensional contribution which is localized in the contraction part between the syringe barrel and the needle

  • The absence of shear thinning effect suggests that no intermediate structures are formed in the bovine serum albumin (BSA) solutions studied in this work

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Summary

Introduction

Macromolecules such as monoclonal antibodies (mAbs) are increasingly being used for treating a large variety of diseases, including immunodeficiency, leukemia and arthritis [17], while globular proteins such as recombinant serum albumin are often employed as drug stabilizers [28, 59]. Perceived pain and back pressure typically limit the highest deliverable volume to 1.5 mL [37, 58, 62]; biopharmaceuticals need to be concentrated above 100 g/L in order for the drug to be effective. Such large values of protein concentrations typically translate into. In order to develop a complete understanding of the origin of the forces arising when a biopharmaceutical drug is delivered by means of SC injection, one must characterize the shear, and the extensional viscosity of concentrated protein solutions. While there is a large amount of works which focus on bulk shear viscosity [29, 36, 53, 68], high-frequency viscoelasticity [42, 43, 65] or interfacial shear rheometry [26, 57] of dense protein solutions, very little attention has so far been paid to the elongational behavior of this category of complex fluids

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