Subcutaneous Injection Volume of Biopharmaceuticals—Pushing the Boundaries

Mathaes, Roman; Koulov, Atanas V.; Joerg, Susanne; Mahler, Hanns‐Christian

doi:10.1016/j.xphs.2016.05.029

Cited by 131 publications

(105 citation statements)

References 35 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…Despite the growing research interest in subcutaneous administration of higher volumes of drugs using a single large dose [17,19,37,38,55], the understanding of the feasibility of longer injection duration for handheld autoinjectors remains limited. The non-interventional simulated use study reported here provides initial empirical insights on the effect of injection duration on user's force as proxy for the user's ability to hold a handheld autoinjector against the skin.…”

Section: Discussionmentioning

confidence: 99%

“…The healthcare industry, however, has started to explore the self-administration of single-dose volumes above 1 mL, thus triggering debate around the feasible limits of injectable volume, methods, and rates for subcutaneous drug administration [2,[17][18][19]. The growing interest in subcutaneous injection of large-volume single doses up to 2 mL or more can be attributed to three major causes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hold the device against the skin: the impact of injection duration on user’s force for handheld autoinjectors

Schneider

Mueller

Jordi

et al. 2019

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

Background: The recent development of high-volume subcutaneous drug delivery using handheld autoinjectors has resulted in longer injection durations. However, the usability of long injections has been neglected. This study aimed to investigate the effects of injection duration on users' ability to apply injections while holding the device against the skin at the injection site. Methods: Thirty-two participants among patients, caregivers, and health-care professionals simulated three injections with different injection durations to evaluate usability and user's force. Linear and quantile regression were then applied to determine the impact of the injection duration on response variables related to user's force. Results: A significant negative effect of injection time was found on both the minimum and mean user's force applied. Initial empirical evidence was also determined on the negative association being more pronounced for users exerting lower force to hold the device against the skin. Conclusions:The results that are subject to future clinical validation suggest the feasibility of injections lasting up to approximately 30 s using handheld autoinjectors. The participants of the simulated use study successfully applied long-duration injections regardless of disease states, age, or visual and dexterity impairments. ARTICLE HISTORY

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hold the device against the skin: the impact of injection duration on user’s force for handheld autoinjectors

Schneider

Mueller

Jordi

et al. 2019

Expert Opinion on Drug Delivery

View full text Add to dashboard Cite

show abstract

“…41 This volume limitation precludes the formulation with therapeutically relevant concentrations of many lipophilic drugs without the use of organic solvents or other solubilizing agents, which may irritate tissues and lead to induration, sloughing, or abscess formation. However, the volume of an SC dose should be less than 2 mL to avoid adverse events at the injection site, such as injection pain and leakage.…”

Section: Subcutaneousmentioning

confidence: 99%

“…However, the volume of an SC dose should be less than 2 mL to avoid adverse events at the injection site, such as injection pain and leakage. 41 This volume limitation precludes the formulation with therapeutically relevant concentrations of many lipophilic drugs without the use of organic solvents or other solubilizing agents, which may irritate tissues and lead to induration, sloughing, or abscess formation. 26,42 If frequent injections are necessary, the injection site should be rotated to allow time for the tissue to recover.…”

Section: Subcutaneousmentioning

confidence: 99%

Rescue therapies for seizure emergencies: New modes of administration

et al. 2018

View full text Add to dashboard Cite

A subgroup of patients with drug-resistant epilepsy have seizure clusters, which are a part of the continuum of seizure emergencies that includes prolonged episodes and status epilepticus. When the patient or caregiver can identify the beginning of a cluster, the condition is amenable to certain treatments, an approach known as rescue therapy. Intravenous drug administration offers the fastest onset of action, but this route is usually not an option because most seizure clusters occur outside of a medical facility. Alternate routes of administration have been used or are proposed including rectal, buccal, intrapulmonary, subcutaneous, intramuscular, and intranasal. The objective of this narrative review is to describe the (1) anatomical, physiologic, and drug physicochemical properties that need to be considered when developing therapies for seizure emergencies and (2) products currently in development. New therapies must consider parameters of Fick's law such as absorptive surface area, blood flow, membrane thickness, and lipid solubility, because these factors affect both rate and extend of absorption. For example, the lung has a 50 000-fold greater absorptive surface area than that associated with a subcutaneous injection. Lipid solubility is a physicochemical property that influences the absorption rate of small molecule drugs. Among drugs currently used or under development for rescue therapy, allopregnanolone has the greatest lipid solubility at physiologic pH, followed by propofol, midazolam, diazepam, lorazepam, alprazolam, and brivaracetam. However, greater lipid solubility correlates with lower water solubility, complicating formulation of rescue therapies. One approach to overcoming poor aqueous solubility involves the use of a water-soluble prodrug coadministered with a converting enzyme, which is being explored for the intranasal delivery of diazepam. With advances in seizure prediction technology and the development of drug delivery systems that provide rapid onset of effect, rescue therapies may prevent the occurrence of seizures, thus greatly improving the management of epilepsy.

show abstract

“…A literature search on the state-of-the-art knowledge on subcutaneous back-pressure was carried out. Five relevant articles were found together with a Ph.D. thesis [2][3][4][5][6][7]. The study by Allmendinger et al calculated the tissue back-pressure by measuring the injection forces during subcutaneous injection [2].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Simulation of Tissue Back-Pressure for Pen Injectors and Auto-Injectors

Yildiz

Lenau

2019

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Purpose: The aim of this project was to show that tissue back-pressure can be measured in vitro using a simple pneumatic model. Methods:A thorough literature study revealed four relevant papers all describing in vivo studies. One of these studies where the subcutaneous tissue back-pressure was determined in 11 patients was used as a reference for the present work. A pneumatic model capable of simulating the back-pressure and the diffusion of drug during subcutaneous injection was developed. The in vitro model was tested using the same type of pen injector as used in the reference study.Results: Comparison of the results revealed that the measured pressure in the in vitro experiments were similar to the subcutaneous tissue back-pressure measured in vivo. G30 0.3 x 8.0 mm and G32 0.23/0.25 x 4.0 mm needles were used for the in vitro experiments, whereas a G31 0.25 x 6.0 mm needle was used for the in vivo experiments. This is one possible explanation of approximately 30 µL/s higher flow rates for the in vitro experiments compared to the in vivo experiment. Conclusion:The low-complexity model allows repeated measurements, and provides a stable data output paving the way for measuring subcutaneous back-pressure in vitro.

show abstract

Subcutaneous Injection Volume of Biopharmaceuticals—Pushing the Boundaries

Cited by 131 publications

References 35 publications

Hold the device against the skin: the impact of injection duration on user’s force for handheld autoinjectors

Hold the device against the skin: the impact of injection duration on user’s force for handheld autoinjectors

Rescue therapies for seizure emergencies: New modes of administration

In Vitro Simulation of Tissue Back-Pressure for Pen Injectors and Auto-Injectors

Contact Info

Product

Resources

About