Development of Hyaluronic Acid Hydrogel of FS-NTF (HA-FS-NTF)

The formulated FS-NTF was embedded into the hyaluronic acid hydrogel by sprinkling it on the pH-induced hyaluronic acid hydrogel. This polymeric hydrogel was prepared with 2% hyaluronic acid using 0.5% Gantrez® S-97 (Mw = 1.2 <sup>×</sup> <sup>10</sup><sup>6</sup> Da) as a cross-linker in a phosphate buffer saline (PBS) media (pH 4.5) maintained at 37 ± 1 ◦C according to preliminary tests which were performed to determine the optimum levels for hyaluronic acid and cross linker. The polymeric mixture was left overnight to hydrate with continuous stirring at 110 rpm. Finally, the HA-FS-NTF was developed by mixing 10 mL of the formulated FS-NTF containing 600 mg of the drug into the prepared hydrogel (100 mL) to obtain the final 0.5% drug containing the transfersomal hydrogel preparation. The FS-NTF was dispersed in water, and this aqueous dispersion was sprinkled over the plain hydrogel base. Because hyaluronic acid has a higher affinity to absorb water molecules and swell, the state of the water in swollen hydrogels is an important factor that influences the absorption and diffusion of solutes through the hydrogel. Generally, water consists of bound water and free water in water-swollen systems. When a hydrogel network begins to swell, the hydrophilic and hydrophobic groups of polymer chains interact with the water molecules, leading to "bound water." Then the network will absorb additional water, due to the osmotic pressure, leading to "free water" that fills the space between the network chains. This HA-FS-NTF was refrigerated at 4 ◦C to 8 ◦C and tested for content uniformity by dividing a certain amount of the formed gel into pieces of equal weight and analyzing these pieces for fluconazole content. After ensuring the content uniformity, further evaluation was done.
