Performance characterization of spring-actuated prefilled pen devices for lebrikizumab and dupilumab.

Background: Design parameters of prefilled pens, known as autoinjectors within the medical device community, can affect pen's functioning and user experience. This study compares the performance of two 2 mL prefilled pen devices: lebrikizumab (125 mg/mL) and dupilumab (150 mg/mL).

Research Design And Methods: We recorded force and acoustic signals during administration from the prefilled pen devices and performed high-speed video recording during needle insertion and drug delivery.

The role of initial lymphatics in the absorption of monoclonal antibodies after subcutaneous injection.

The subcutaneous injection is the most common method of administration of monoclonal antibodies (mAbs) due to the patient's comfort and cost-effectiveness. However, the available knowledge about the transport and absorption of this type of biotherapeutics after subcutaneous injection is limited. Here, a mathematical framework to study the subcutaneous drug delivery of mAbs from injection to lymphatic uptake is presented.

Clinical Investigation of Large Volume Subcutaneous Delivery up to 25 mL for Lean and Non-Lean Subjects.

Purpose: To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects.

Methods: A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness.

Hydrodynamic considerations for spring-driven autoinjector design.

In recent years, significant progress has been made in the studies of the spring-driven autoinjector, leading to an improved understanding of this device and its interactions with tissue and therapeutic proteins. The development of simulation tools that have been validated against experiments has also enhanced the prediction of the performance of spring-driven autoinjectors. This paper aims to address critical hydrodynamic considerations that impact the design of spring-driven autoinjectors, with a specific emphasis on sloshing and cavitation.

The role of liquid rheological properties on the injection process of a spring-driven autoinjector.

Accurate injection time prediction is essential in developing spring-driven autoinjector devices since the drug delivery is expected to finish within seconds to bring convenience, reduce the risk for early lift-off, and provide a consistent experience to users. The Carreau model captures the liquid's shear-dependent viscosity measured in our experiments. Thus, a quasi-steady model, which uses the Carreau model to describe the liquid's viscosity, is developed to predict the injection time of spring-driven autoinjectors.

Modeling cavitation bubble dynamics in an autoinjector and its implications on drug molecules.

The collapse of cavitation bubbles induced by abrupt acceleration of the syringe in an autoinjector device can lead to protein aggregation. The details of bubble dynamics are investigated using an axisymmetric, three-dimensional simulation with passive tracers to illustrate the transport of protein molecules. When a bubble near the syringe wall collapses, protein molecules are concentrated in the re-entrant jet, pushed towards the syringe wall, and then spread across the wall, potentially leading to protein adsorption on the syringe wall and aggregation.

Subcutaneous Injection Site Pain of Formulation Matrices.

Purpose: The objective of this work was to systematically evaluate the effects of formulation composition on subcutaneous injection site pain (ISP) using matrices comprising of common pharmaceutical excipients.

Methods: Two randomized, blinded, crossover studies in healthy subjects were conducted at a single site, where subjects received 1 mL SC injections of the buffer matrices. ISP intensity was measured using a 100 mm visual analogue scale (VAS), which was then analyzed via heatmap, categorical grouping, subgroup analysis, and paired delta analysis.

The Interface Motion and Hydrodynamic Shear of the Liquid Slosh in Syringes.

Purpose: Interface motion and hydrodynamic shear of the liquid slosh during the insertion of syringes upon autoinjector activation may damage the protein drug molecules. Experimentally validated computational fluid dynamics simulations are used in this study to investigate the interfacial motion and hydrodynamic shear due to acceleration and deceleration of syringes. The goal is to explore the role of fluid viscosity, air gap size, syringe acceleration, syringe tilt angle, liquid-wall contact angle, surface tension and fill volume on the interface dynamics caused by autoinjector activation.

Physicochemical Excipient-Container Interactions in Prefilled Syringes and Their Impact on Syringe Functionality.

Previous studies have shown that parenteral formulation excipients can interact with the silicone oil in prefilled syringes, thereby causing variations in glide force that affect the performance of autoinjectors. Thus, it is crucial to control the glide force of the prefilled syringes to mitigate the potential risk of dose inaccuracies. This study provided a systematic understanding of the chemical interactions between the excipients, physical interactions between the excipients and the container, as well as their impact on the functional performance of prefilled syringes.

Subcutaneous Injection Performance in Yucatan Miniature Pigs with and without Human Hyaluronidase and Auto-injector Tolerability in Humans.

Recombinant human hyaluronidase PH20 (rHuPH20) facilitates subcutaneous (SC) delivery of co-administered therapeutic agents by locally and transiently degrading hyaluronan in the SC space, and can be administered with therapeutics using a variety of devices. Two SC delivery studies were carried out to assess auto-injector (AI) performance, each in 18 Yucatan miniature pigs. Abdominal injections were administered using three auto-injectors of 1 mL (AI1) and 2 mL (AI2 and sAI2) with different injection speeds and depths (5.

An experimentally validated dynamic model for spring-driven autoinjectors.

This study focuses on developing a predictive dynamic model for spring-driven autoinjectors. The values of unknown physical parameters, such as the heat convection coefficient and the friction force between the plunger and the syringe barrel, are obtained by fitting the experimentally measured displacements of the plunger and the syringe barrel. The predicted kinematics of the components, such as the displacement and velocity of the syringe barrel, agree well with the experiments with a l-norm error smaller than 10%.

Plasma Polymerized HMDSO Coatings For Syringes To Minimize Protein Adsorption.

Current parenteral containers used for the storage and delivery of protein-based drugs, contain silicone oil which may seep into the protein solution and can result in adsorption, aggregation and denaturation of the protein. Tightly adherent surface coatings prepared by radio frequency glow-discharge (RFGD) plasma polymerization are described in this paper. Using this robust technique, methacrylic acid (MA) (hydrophilic), hexamethyldisiloxane (HMDSO) (hydrophobic), tetraglyme (TG) (hydrophilic) were plasma polymerized onto glass.

Drug Formulation Impact on Prefilled Syringe Functionality and Autoinjector Performance.

Given the surging interest in developing prefilled syringe and autoinjector combination products, investment in an early compatibility assessment is critical to prevent unwarranted drug/container closure interactions and avoid potential reformulation during late stages of drug development. In addition to the standard evaluation of drug stability, it is important to consider container closure functionality and overall device performance changes over time because of drug-container closure component interaction. This study elucidated the mechanisms that cause changes in syringe glide force over time and the impact on the injection duration.

Impact of Surfactants on the Functionality of Prefilled Syringes.

Previous studies revealed the impact of formulation factors (excipients and pH) on the functionality of prefilled syringes. Surfactant, a critical formulation component for therapeutic proteins and antibodies, aids in minimizing protein adsorption onto interfaces and reduces protein aggregation or particulate formation. This study evaluated the impact of different surfactants and protein concentration on the functionality of prefilled syringes.

Performance characterization of spring actuated autoinjector devices for Emgality and Aimovig.

Autoinjectors are a convenient and efficient way to self-administer subcutaneous injections of biopharmaceuticals. Differences in device mechanical design can affect the autoinjector functionality and performance. This study investigates the performance differences of two single-spring-actuated autoinjectors.

Two Contrasting Failure Modes of Enteric Coated Beads.

This study aimed to elucidate the mechanisms and kinetics of coating failure for enteric coated beads exposed to high-humidity conditions at different storage temperatures. Enteric coated beads were placed on high-humidity conditions (75 to 98% relative humidity (RH)) in the temperature range of 5 to 40°C. These stability samples of beads were tested for acid dissolution and water activity and also analyzed with SEM, X-ray CT, and DMA.

Impact of Drug Formulation Variables on Silicone Oil Structure and Functionality of Prefilled Syringe System.

Use of prefilled syringes to self-administer biologics via subcutaneous administration provides convenience to patients. The barrel interior of prefilled syringes is typically coated with silicone oil for lubrication to aid plunger movement at the time of administration. This study intended to evaluate the impact of formulation variables on the silicone oil on the barrel interior surface.