What is Cingal?
Cingal is a single-injection combination product administered via intra-articular injection. It contains two active components, cross-linked hyaluronic acid and triamcinolone hexacetonide, formulated together in a single pre-filled syringe.
Active Components
Cingal is a single-injection combination injection containing:
Cross-linked Hyaluronic Acid (HA)
88 mg / 4 mL · 22 mg/mL1
Non-animal derived via bacterial fermentation. Cross-linked to increase stability and extend intra-articular residence time.2
Triamcinolone Hexacetonide (TH)
18 mg / 4 mL · Micronised ≤15 µm (avg 1–4 µm)9
Micronised and stabilised within the HA gel. Low aqueous solubility supports sustained local intra-articular activity.8
It is indicated for the relief of pain, stiffness and functional limitation associated with knee osteoarthritis.1
The Science Behind Cingal
Biological Considerations of Hyaluronic Acid (HA)
The HA component of Cingal is:
- High molecular weight within a biologically relevant range3,4
- Cross-linked to increase stability and slow degradation2
- Present at a high concentration (22 mg/mL) to support joint lubrication1
- Acquired via bacterial fermentation (non-animal derived)1
HA contributes to joint homeostasis through the following mechanisms:
- Lubrication of articular surfaces1
- Shock absorption during joint loading1
- Temporary supplementation of synovial fluid viscoelastic properties1
- Binding to synoviocyte receptors, supporting endogenous HA production4
These mechanical properties are associated with reduced pain and stiffness in patients with knee OA.2
These effects are considered relevant to the temporary restoration of joint homeostasis following intra-articular HA injection, and the findings have been demonstrated in preclinical and clinical studies.1,5
Role of Cross-Linking in Cingal
Cross-linking plays a role in maintaining stability of the TH suspension within the formulation.1
Increases stability6
Chemical cross-links bind adjacent HA chains, forming a three-dimensional polymer network.
Slows enzymatic degradation2
Cross-linking protects HA polymer chains from rapid enzymatic breakdown in the joint environment.
Extends intra-articular residence time7
Supporting the sustained HA effect and maintaining the TH suspension within the formulation.1
Triamcinolone hexacetonide (TH)
Triamcinolone hexacetonide is characterised by:
| Characteristic | Detail |
|---|---|
| Aqueous solubility | Low (relative to other injectable corticosteroids)8 |
| Receptor binding affinity | High within joint tissues8 |
| Anti-inflammatory duration | Approximately 21 days8 |
| Particle size (micronised) | ≤15 µm (average 1–4 µm)1 |
| Formulation | Stabilised within HA gel (uniform suspension, prevents aggregation)1 |
| Dose per syringe | 18 mg / 4 mL1 |
In Cingal, TH is micronised to a particle size of ≤15 µm (average 1–4 µm) and stabilised within the HA gel matrix to maintain a uniform suspension and prevent particle aggregation.1
Chondrocyte Response and Cartilage Considerations
Concerns regarding corticosteroid exposure and cartilage health have been reported in the literature, particularly with repeated high-dose steroid injections.
In vitro studies using inflamed human chondrocytes have shown that:
Finding 1:
HA combined with TH maintains anti-inflammatory activity.5
Finding 2:
The presence of HA may reduce negative cellular effects observed with corticosteroid exposure alone.5
These findings are based on laboratory models and provide mechanistic insight rather than direct clinical outcomes.5
How Cingal Works
Both components act simultaneously following intra-articular injection, addressing dual aspects of knee OA symptoms: the acute inflammatory component and the chronic mechanical component.
Phase 1 Rapid Onset
Triamcinolone Hexacetonide (TH)
Rapidly suppresses inflammation
Triamcinolone hexacetonide exerts anti-inflammatory effects through suppression of inflammatory mediators within the joint. Its low aqueous solubility contributes to prolonged intra-articular residence and sustained local activity.10,11Pain relief begins within days of injection.12
Onset: within days, active ~21 days8,12
Phase 2 Sustained Relief
Cross-linked Hyaluronic Acid
Restores synovial fluid viscoelasticity
HA restores the rheological properties of osteoarthritic synovial fluid, supporting joint lubrication and shock absorption. Cross-linking extends intra-articular residence time, maintaining mechanical benefit through the subsequent weeks and months.1,12
Sustained benefit: up to 6 months12
Together: rapid onset and sustained relief in a single injection
Cingal’s formulation is designed to address both the acute and chronic dimensions of OA symptoms with TH bridging the early post-injection period while HA provides the extended mechanical benefit.1,12
1 Instructions for Use. Cingal. Anika Therapeutics. [Refer to current IFU for full approved indications.]
2 Data on file (R09-030 Technical Report Degradation Test Method for Joint Health Products)
3 Smith MM, Ghosh P. The synthesis of hyaluronic acid by human synovial fibroblasts is influenced by the nature of the hyaluronate in the extracellular environment. Rheumatol Int. 1987;7(3):113-22. doi: 10.1007/BF00270463. PMID: 3671989.
4 Nicholls MA, et al. Disease modifying effects of hyaluronan in OA. Clin Med Insights Arthritis Musculoskelet Disord. 2017
5 Bauer C, et al. Increased chondroprotective effect of HA combined with glucocorticoid. Biomedicines. 2022.
6 Data on file (R09-041 Chemical Stability Evaluation of Cross-linked Hyaluronic Acid and Triamcinolone Hexacetonide in Cingal™ Product)
7 Injection Regimen of Sequential Corticosteroid and Hyaluronic Acid Injections. Etienne L Belzile, Robert T Deakon, Christopher Vannabouathong, Mohit Bhandari, Martin Lamontagne and Robert McCormack
8 Stephens M., et. al. Musculoskeletal Injections: A Review of the Evidence. Am Fam Physician. 2008 Oct 15;78(8):971-976
9 Data on File, Anika Therapeutics, Inc
10 Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-. Pharmacology of intra-articular triamcinolone. 2014. Available from: https://www.ncbi.nlm.nih.gov/books/NBK258920/
11 Dharmanand et al., Role of Intra-Articular Triamcinolone Hexacetonide… (2025), particularly for the discussion of slower systemic release, prolonged joint retention, and sustained effect. [journals.sagepub.com](opens in a new tab)
12 Hangody L, et al. Intraarticular injection of a cross-linked sodium hyaluronate combined with triamcinolone hexacetonide (Cingal) to provide symptomatic relief of osteoarthritis of the knee: a randomized, double-blind, placebo-controlled multicenter clinical trial. Cartilage. 2018 Jul;9(3):276-283. doi: 10.1177/1947603517703732. Epub 2017 May 23.
13 Data on File – 16-02
14 Data on file – 19-01
15 Data on File – 13-02
For full prescribing information and Instructions for Use, visit anikaifu.com(opens in a new tab)
