Trial reportPharmaceutical research2021
Subcutaneous Injection Site Pain of Formulation Matrices.
Trial report in Pharmaceutical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- Spotlight on Clinical In-Use Parameters for Intravenous Infusion of Therapeutic Antibodies: A Systematic Review.Pharmaceutical research · 2025Pooled it
- A Systematic Literature Review of Injection Site Pain Perception in Adult Patients Treated with Citrate-Free and Citrate-Containing Biologic Agents.Current rheumatology reviews · 2023Pooled it
- One Subcutaneous 2-ml Injection of Mirikizumab is Bioequivalent to Two 1-ml Subcutaneous Injections in Healthy Participants.Advances in therapy · 2026Trial
- Clinical Evaluation of the Temperature Dependence of Subcutaneous Injection Experience in Healthy Volunteers.Pharmaceutical research · 2025Trial
- An Investigation Into Local Infusion Site Pain After Infusion of Ultra Rapid Lispro Excipients Across Sites and Depths.Journal of diabetes science and technology · 2024Trial
- From permeation enhancer to therapeutic enabler: Advances, applications, and translational perspectives in hyaluronidase-based drug delivery.Materials today. Bio · 2026Review
- Monoclonal antibody formulations: a quantitative analysis of marketed products and patents.mAbs · 2025Article
- Pharmacokinetic Comparability and Safety Between Original and Citrate-Free Mirikizumab Formulations for Subcutaneous Injections: Results from Three Clinical Trials.Advances in therapy · 2025Article
- Optimization of therapeutic antibodies for reduced self-association and non-specific binding via interpretable machine learning.Nature biomedical engineering · 2024Article
- Unveiling the Rational Development of Stimuli-Responsive Silk Fibroin-Based Ionogel Formulations.Chemistry of materials : a publication of the American Chemical Society · 2023Article
- Factors Affecting Performance of Insulin Pen Injector Technology: A Narrative Review.Journal of diabetes science and technology · 2023Review
- Ionic Liquid-Based Strategy for Predicting Protein Aggregation Propensity and Thermodynamic Stability.JACS Au · 2022Article
- Real-world data on switching from intravenous to subcutaneous vedolizumab treatment in patients with inflammatory bowel disease.Alimentary pharmacology & therapeutics · 2022Article
- Development of an Insulin Pen is a Patient-Centric Multidisciplinary Undertaking: A Commentary.Journal of diabetes science and technology · 2022Article
- New insight into the importance of formulation variables on parenteral growth hormone preparations: potential effect on the injection-site pain.Frontiers in endocrinology · 2022Review
- Multi-Electrode Array of Sensory Neurons as an In Vitro Platform to Identify the Nociceptive Response to Pharmaceutical Buffer Systems of Injectable Biologics.Pharmaceutical research · 2021Article
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Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe 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.
methodsTwo 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.
resultsBuffer type, buffer concentration and tonicity agent showed a substantial impact on ISP. Citrate buffer demonstrated a higher ISP than acetate buffer or saline). The 20 mM citrate buffer was more painful than 10 or 5 mM citrate buffers. NaCl and propylene glycol were significantly more painful than sugar alcohols (mannitol, sucrose, trehalose or glycerol). Histidine buffers exhibited ISP in the descending order of 150 mM > 75 mM > 25 mM > 0 mM NaCl, while histidine buffers containing Arginine-HCl at 0, 50, or 150 mM all showed very low ISP. Histidine buffer at pH 6.5 showed a lower ISP than pH 5.7.
conclusionsThis systematic study via orthogonal analyses demonstrated that subcutaneous ISP is significantly influenced by solution composition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.