Are you formulating a pharmaceutical product, a medical device or a dermo-cosmetic solution based on hyaluronic acid? Before comparing suppliers, one fundamental question must guide your raw material selection: what molecular weight / viscosity is appropriate for your application?
It is one of the most decisive parameters in the performance of your finished product.
In this article, we will be looking at the different types of hyaluronic acid and giving you some examples of how they are used. We hope this will help you to better understand the subject and choose the product best suited to your business and research.
What Is the Molecular Weight of Hyaluronic Acid?
Hyaluronic acid (HA) is a natural polymer composed of repeating units of N-acetylglucosamine and glucuronic acid. It is precisely the length of this polymer chain that defines its molecular weight, expressed in Daltons (Da) or kiloDaltons (kDa).
The range is extremely wide: from 5,000 Da to over 5,000,000 Da depending on the production process.
This range of molecular weights gives HA a variety of physicochemical and biological properties that influence its behaviour and effectiveness in different applications.
Molecular Weight and Viscosity: A Direct and complex Relationship
Molecular weight is directly correlated with the viscosity of the HA solution.
Generally speaking, when high-molecular-weight hyaluronic acid (HA) is used to create a hydrogel, the resulting solution has a high viscosity. Conversely, if the molecular weight is low and the HA is used at the same mass concentration, the solution will be more fluid. Thus, the mechanical behaviour of the gel can be easily adapted to the intended application. It should also be noted that other parameters can also influence the viscosity of a hydrogel
Beneath this apparent simplicity lies a potential difficulty. Indeed, it is not particularly easy to measure the molecular weight of a hyaluronic acid sample directly. Techniques such as Size Exclusion Chromatography with Multi-angle Light Scattering (SEC-MALS) can be used, but they require good chromatographic separation and can be disrupted by factors such as molecular aggregation.
So how can this be done more simply on a routine basis?
The Mark-Houwink equation describes the empirical relationship between its molecular weight and another characteristic parameter of a polymer : intrinsic viscosity. It uses two constants that depend on the polymer, the solvent used and the temperature. These constants can be found in literature and may vary considerably within the same molecular weight range. They can then be determined using SEC-MALS method.
This is why the European Pharmacopoeia monograph on sodium hyaluronate recommends viscosity testing, a harmonised and more reproducible method.
This viscosity parameter allows for a rigorous comparison of HA products with one another, unlike molecular weight, whose values are more variable from one product to another, preventing any reliable comparison.
A reliable supplier must be able to guarantee:
- A defined and reproducible viscosity range for each product in its range
- Intrinsic viscosity data available in the certificate of analysis
- A validated analytical method compliant with the requirements of the European Pharmacopoeia
At Teknolike, we produce pharmaceutical-grade HA via fermentation, enabling us to control parameter variability and achieve reproducible and reliable viscosity results. Each batch is tested in accordance with the European Pharmacopoeia. Intrinsic viscosity is systematically included in our certificates of analysis.
Physico-chemical behaviour according to viscosity category
High intrinsic viscosity HA (> 3.5 m3/kg)
High-viscosity HA has strong viscoelastic properties. In aqueous solution, it forms a dense three-dimensional network that provides a significant mechanical effect and exceptional water-retention capacity. It is resistant to enzymatic degradation.
Biologically, it has recognised anti-inflammatory properties and good tissue tolerance. It plays a pivotal role in wound healing. It is absorbed little or not at all in its native form through biological membranes, making it the material of choice for applications in direct contact with internal tissues.
Preferred industrial applications :
- Intra-articular injectables (viscosupplementation for osteoarthritis treatment)
- Surgical ophthalmic viscoelastics (cataract, anterior segment surgery), …)
- Dermal filling gels (aesthetic fillers)
- Vitreous substitutes in ophthalmology
Low and Medium intrinsic viscosity HA (between 1 and 3,5 m3/kg)
Products formulated using HA with medium or low intrinsic viscosity have a radically different profile. They are less viscous and do not possess the same mechanical properties. Their shorter polymer chain gives them better tissue penetration and increased solubility in aqueous formulations.
Biologically, it has active biological effects: it stimulates cell proliferation, promotes neovascularisation and exhibits pro-angiogenic properties useful in certain dermatological and wound-healing applications.
Preferred industrial applications :
- Topical dermo-cosmetic formulations (serums, moisturising creams, masks, dermatological products targeting skin regeneration, …)
- Dermal fillers and volume-restoring products (cosmetic fillers)
- Vesical (urology) and gastroenterological formulations (intestinal mucosal protection, …)
- Ophthalmic formulations (eye drops for dry eye syndrome)
- Food supplements for joint health and skin hydration
How to Choose the Right Grade for Your Application: A Practical Guide
Here are the key criteria to guide your selection:
- Start by defining your route of administration and your expected mode of action
- Identify the regulatory constraints applicable to your finished product
- Evaluate the rheological profile required by your application and consequences on you manufacturing process
- Request samples and carry out preliminary trials
- Validate batch-to-batch reproducibility
Key Takeaways: intrinsic viscosity of your raw material is a Formulation parameter not to overlook
The intrinsic viscosity / molecular weight of hyaluronic acid is a fundamental parameter that determines the physicochemical properties, biological behaviour and clinical efficacy of your finished product.
A poor grade selection can compromise the performance of your formulation, complicate your manufacturing process and weaken your regulatory dossier.
Choosing a supplier capable of guaranteeing rigorous, reproducible results with traceability is therefore a decision as strategic as the grade selection itself.
Choose Teknolike to meet your needs
Choosing a reliable supplier is crucial, as it affects the purity and reproducibility of the product supplied.
Opting for a bacterial fermentation production process yields a pure product with specific viscosity ranges. If purification is not carried out correctly, there is a risk of contamination by protein impurities, which can lead to significant immune reactions.
Teknolike dedicates time to optimising its fermentation process in order to better control this variability, to obtain a product with consistent purity and viscosity, and to produce similar results across various applications.
Teknolike develops a comprehensive range of sodium hyaluronate covering the full range of viscosities to meet the specific requirements of each market and formulation.
Choosing Teknolike means choosing a genuine technical partnership to reduce your clinical risks.
All our products are:
- Pharmaceutical grade, compliant with the European Pharmacopoeia
- Produced by bacterial fermentation in full compliance with GMP
- Supplied with detailed certificates of analysis, signed by the qualified person
- Available as samples for your preliminary trials
Our technical team is available to assist you in selecting the grade best suited to your application and your manufacturing process.
Are you interested in establishing a close technical partnership? Contact our technical team they will support you at every stage of your development.