Subcutaneous drug delivery: An evolving enterprise

Jones, Graham B.; Collins, D. M.; Harrison, Michael W.; Thyagarajapuram, Nagarajan R.; Wright, Justin M.

doi:10.1126/scitranslmed.aaf9166

Cited by 58 publications

(43 citation statements)

References 8 publications

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“…The barriers of SC absorption include passage through tissues at the injection site to the vascular or lymphatic systems, permeation through the vascular endothelial cells, local enzymatic degradation, and loss to the endocytosis and phagocytosis. 1,13,[26][27][28][29][30] Other factors including molecule size (weight), charge, lipophilicity, transporter uptakes, formulation, and protein binding can also play a role in a compound's diffusion and absorption process. [26][27][28][29][30] Moreover, formulation properties such as formulation vehicles, pH, ionic strength, and viscosity can have an additional impact on drug distribution.…”

Section: Resultsmentioning

confidence: 99%

“…1,13,[26][27][28][29][30] Other factors including molecule size (weight), charge, lipophilicity, transporter uptakes, formulation, and protein binding can also play a role in a compound's diffusion and absorption process. [26][27][28][29][30] Moreover, formulation properties such as formulation vehicles, pH, ionic strength, and viscosity can have an additional impact on drug distribution. Based on all the aforementioned factors, we concluded that unlike oral dosing, in which drug absorption can be reasonably predicted on the basis of physicochemical properties, 19 modeling and predicting exposure following SC dosing will need to be based on the in vivo testing of each compound individually.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

Chiang¹,

Nagapudi²,

Fan³

et al. 2019

Journal of Pharmaceutical Sciences

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

Chiang¹,

Nagapudi²,

Fan³

et al. 2019

Journal of Pharmaceutical Sciences

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“…Protein-based medications are not compatible with oral administration [10], and etanercept is therefore administered via subcutaneous (SC) injection [6]. SC administration is an effective method for delivering medications slowly and at a sustained rate, as fatty SC tissue allows uptake of large proteins via the lymphatic system [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A Randomized Controlled Trial

et al. 2019

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Introduction Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration. Methods This phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect. Results A total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference − 4 mm; 95% confidence interval: − 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed. Conclusions The new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation. Trial Registration ClinicalTrials.gov: NCT02986139. Funding Amgen Inc, Thousand Oaks, CA USA.

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“…Subcutaneous administration of drugs is driving changes in global health-care systems [1,2]. In particular, novel device designs enable patient-centered concepts to healthcare and allow users across chronic disease states to routinely self-inject drugs at home, thereby eliminating the need of going to a hospital or infusion center [3][4][5][6][7].…”

Section: Introductionmentioning

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%

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

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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

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Subcutaneous drug delivery: An evolving enterprise

Abstract: Recent advances in subcutaneous drug delivery and device design are transforming the biopharmaceutical sector and improving patient care.

Cited by 58 publications

References 8 publications

Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

Investigation of Drug Delivery in Rats via Subcutaneous Injection: Case Study of Pharmacokinetic Modeling of Suspension Formulations

Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rheumatoid Arthritis or Psoriatic Arthritis Patients: A Randomized Controlled Trial

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

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