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.
Let’s explore together the different types of hyaluronic acid available and some application examples. This will help you understand and select the most suitable raw material for your activities and research and thereby support your sales.
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. The length of this polymer chain determines 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 diversity of molecular weights gives HA a variety of physicochemical and biological properties, which influence its behavior 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.
In general, when a high-molecular-weight HA is used to form a hydrogel, the resulting solution exhibits high viscosity. Conversely, if the molecular weight is low and HA is used at the same mass concentration, the solution will be more fluid. Thus, the mechanical behavior of the gel can be easily adjusted according to the intended application. It should also be noted that other parameters can also influence the viscosity of a hydrogel.
Behind this apparent simplicity lies a potential challenge. It is not easy to directly measure the molecular weight of a hyaluronic acid sample. 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 affected, for example, by 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 incorporates two constants dependent on the polymer, the solvent used, and the temperature. These values can either be found in publications (though they can vary significantly within the same molecular weight range), or they can also be determined by SEC-MALS.
This is why the European Pharmacopoeia monograph on HA recommends controlling intrinsic viscosity, a harmonized and more reproducible method.
This intrinsic viscosity parameter makes it possible to rigorously compare different HAs, unlike molecular weight, whose values are more variable from one raw material to another, reducing the reliability of direct comparisons.
A trustworthy supplier should therefore 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 European Pharmacopoeia requirements.
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 intrinsic viscosity HA has strong viscoelastic properties. In aqueous solution, it forms a dense three-dimensional network that gives the resulting viscoelastic solution significant mechanical effects as well as increased water retention capacity. In addition, the solution is somewhat less sensitive to enzymatic degradation than more fluid solutions.
From a biological standpoint, high intrinsic viscosity HA has well-recognized anti-inflammatory properties and good tissue tolerance. It plays a key role in wound healing. It is little or not absorbed in its native form across biological membranes, making it the reference material for injectable applications.
Preferred industrial applications :
- Intra-articular injectables (viscosupplementation for the treatment of osteoarthritis).
- Viscoelastic ophthalmic surgical products (cataract surgery, anterior segment surgery, etc.), and vitreous substitutes
- Dermal filling gels (aesthetic fillers)
Low and Medium intrinsic viscosity HA (between 1 and 3,5 m3/kg)
Products formulated with medium or low intrinsic viscosity HA present a radically different profile. They are less viscous and do not exhibit the same mechanical properties as viscoelastic solutions made from high intrinsic viscosity HA. A shorter HA polymer may provide better tissue penetration and increased solubility in aqueous formulations.
From a biological standpoint, the shorter HA polymer exerts active biological effects: it can stimulate cell proliferation, promote neovascularization, and exhibit pro-angiogenic properties that are useful in certain dermatological and wound-healing applications.
Preferred industrial applications :
- Topical dermocosmetic formulations (serums, moisturizing creams, masks, dermatological products intended for skin regeneration, etc.).
- Dermal filling and volumizing products (aesthetic fillers).
- Dietary supplements focused on hydration and joint health.
How to choose the right characteristics for your HA: a practical guide
Here are the main criteria to consider when making your choice:
- First, define your route of administration and expected mode of action.
- Identify the regulatory constraints applicable to your finished product
- Assess the rheological profile required by your application and its impact on your manufacturing process.
- Request samples and carry out preliminary trials
- Validate batch-to-batch reproducibility
In summary: the intrinsic viscosity of your raw material is a formulation parameter that should not be overlooked
The intrinsic viscosity / molecular weight of hyaluronic acid is a fundamental parameter that determines the physicochemical properties, biological behavior, and clinical efficacy of your finished product.
An incorrect choice of HA characteristics upstream can compromise the performance of your formulation, complicate your manufacturing process, and weaken your regulatory dossier.
Choosing a supplier capable of guaranteeing rigorous, reproducible control with full traceability is therefore a strategic decision, just as important as selecting the raw material typology itself.
Choosing Teknolike to meet your application needs
Choosing a reliable supplier is crucial, as it influences the purity and reproducibility of the characteristics of the supplied raw material, thereby strengthening the safety profile of your finished product.
Selecting a bacterial fermentation production process makes it possible to obtain a pure product with specific intrinsic viscosity ranges. When purification is not properly performed, there is a risk of contamination by various impurities, which may trigger significant immune reactions.
Teknolike has devoted considerable time to optimizing its fermentation process in order to fully control this potential variability, achieving a raw material with consistent purity and viscosity while delivering similar results across various applications.
Teknolike develops a comprehensive range of sodium hyaluronate (HA) covering all viscosity ranges to meet the specific requirements of each market and formulation.
Choosing Teknolike means choosing a true technical and commercial partnership to optimize your therapeutic offerings.
All our products are:
- Pharmaceutical grade, compliant with the European Pharmacopoeia
- Produced by bacterial fermentation in compliance with GMP standards
- Accompanied by detailed Certificates of Analysis signed by the Qualified Person
- Available as samples for your preliminary testing
Our technical teams are at your disposal to support you in selecting the most suitable characteristics for your application and manufacturing process.
Would you like to initiate a more in-depth technical collaboration?
Please contact our teams, who will support you at every stage of your development.