Hydrogels offer an interesting way to administrate active pharmaceutical ingredients (API). Recently, polaxamer polymers have been used for hydrogel applications. This type of triblock copolymer is composed of a central hydrophobic polyoxypropylene and two hydrophilic polyoxyethylene outer blocks. This structure confers an amphiphilic behavior like that of surfactants. Depending on the length of each block, properties such as gel and micelle formation can be tuned. They are also known under registered names, such as Pluronic®, Kolliphor®, or Synperonic®. The success of these polymers is related to the many advantages they offer:
- Easiness of use alone or in a mixture.
- Biocompatibility – in the GRAS list (General Recognized As Safe).
- Versatile administration – Injection, topical, rectal, …
- Adaptive- amphiphilic structure able to uptake hydrophilic and lipophilic APIs.
- Thermosensitive – allows triggering compound release with temperature.
A research group at the University of Catanzaro, Italy, has recently proposed hydrogel based on polaxamer 407 for topical and parenteral administration. In both cases, hydrogels for different applications, such as topical creams or injections, are proposed. In two articles they describe a straightforward procedure for the development of a polaxamer-based formulation. This approach consists of three simple and rapid steps:
- The preparation at 4°C mixing all excipients in a liquid state
- The formation of the hydrogel at room temperature by increasing the temperature above a critical point.
- Complete and fast characterization of the key parameters of the gel, i.e. stability, gelation, and flow rheology
In the first step, all excipients are mixed at 4°C. As the aqueous polaxamer dispersion forms a micellar solution at 4°C, it is possible to solubilize both, lipophilic and hydrophilic ingredients.
The gelation occurs above a certain temperature, which depends on the concentration and the length of the polaxamer. Most of the polaxamers form gels at room temperature and above, ideal for topical applications.
The evaluation and suitability of the polaxamer preparation are studied with three techniques as shown in the graph here below:
Figure 1. Scheme of polaxamer preparation
- Turbiscan (Formulaction, France) studies the stability and thus the compatibility of the different excipients. Although polaxamers are highly versatile, it is very important to avoid any incompatibility issues, which may reduce the efficiency of the product. Turbiscan technology allows for evaluation stability rapidly thanks to the high resolution during scanning.
- Rheolaser Master (Formulaction, France) studies microrheology, i.e. the viscoelastic properties at rest. As for global stability, excipients may interfere with the gelation properties. It was shown that samples with too low polaxamer concentrations do not form a gel correctly. The optical DWS technology allows measuring at rest and helps therefore in aging experiments to evaluate the viscoelastic properties of the gel formulations.
- Flow rheology with a conventional rheometer allows for studying the viscoelastic properties under stress. This is of particular interest when dealing with topical or parenteral applications. A minimum viscosity is needed to keep the cream on the skin, thus the active compound. If the viscosity is too low under the shear of spreading, the cream may flow away. Measurements of viscosity under different shear rates confirm the potential application.
References and related articles for more information:
- Hydrogel characterization techniques: Cristiano, M.C.; Froiio, F.; Mancuso, A.; De Gaetano, F.; Ventura, C.A.; Fresta, M.; Paolino, D. The Rheolaser Master™ to Evaluate the Influence of Topical Drug Delivery Systems on Rheological Features of Topical Poloxamer Gel. Molecules 2020, 25, 1979. https://doi.org/10.3390/molecules25081979
- Example of an innovative hydrogel for inkection purposes: Giuliano, E.; Paolino, D.; Cristiano, M.C.; Fresta, M.; Cosco, D. Rutin-Loaded Poloxamer 407-Based Hydrogels for In Situ Administration: Stability Profiles and Rheological Properties. Nanomaterials 2020, 10, 1069. https://doi.org/10.3390/nano10061069