A research scientist explains the decisions that go into designing a dual-chamber drug-delivery device.

Amy Heintz

Dual-chamber systems are of growing interest for enabling drug delivery in multiple settings. In the self-administration drug delivery market, they can reduce the number of handling steps and the potential for error by the patient or caregiver during drug reconstitution. In a wound healing or surgical setting, dual-chamber systems can decrease the time to table for reconstitution or other mixing steps. They also provide a means to simultaneously deliver two independent liquid molecules.  

There are several dual-chamber design options that can be classified by how the two compartments are mixed. Traditional dual-chamber systems incorporate a bypass position, where the plunger moves into a groove bypass to allow the two compartments to mix.  Newer designs incorporate a plunger valve that separates the components during storage but creates an open delivery path upon activation. These devices most often use a standard cartridge or syringes while some emerging devices employ novel arrangements, such as a tip that can be added to a syringe or a plunger within a plunger. Other incipient devices incorporate microfluidic channels to enhance mixing.

In selecting and validating the best dual-chamber design option for the delivery of a given pharmaceutical, the device designer must balance a complex set of requirements and trade-offs. For example, design features that allow the formulations inside these dual chamber syringes to be rapidly dispensed can often provide a failure point if the design features implemented to separate the syringe contents are not properly employed.

It is important to understand all the material interfaces and how they can change and age in different scenarios including sterilization, shipment, storage, and use. The goal is to ensure that environmental, chemical, thermal, and/or pressure variations do not push the properties outside the requirements window. Key concerns often include:

Without adequate accommodation of how material aging influences properties, these devices can exhibit premature failures.

In our experience, one element that is often overlooked is the material properties of the plunger and how it interacts with the syringe, which may be lubricated.  Two important attributes are its surface properties (roughness and energy) and viscoelasticity. The surface morphology is critical in determining how the static pressure evolves, as well as the potential for leak paths. We have found that it is important to characterize roughness and surface energy, and their lot to lot variation, for all system components.

The viscoelastic response of the plunger is also important in dictating sealing and frictional forces. Over time, the material's relaxation spectra will allow the material to plastically deform, increasing the potential contact area involved in the seal and the stress applied to any lubrication layer. Viscoelastic properties at the elastomer surface will dominate the relaxation/ deformation process and may vary substantially from the bulk, varying with manufacturing process, thermal history, sterilization, and chemical exposure. 

Ultimately, the best design for these devices will be a compromise that best meets the use conditions.

Amy Heintz is Senior Research Scientist at Battelle. 

[Image courtesy of BLACKZHEEP/FREEDIGITALPHOTOS.NET]