Using Solid Dispersion (SD) Technology to Enhance Solubility and Further Integrate SD Into Hydrogel for Topical Econazole Nitrate Delivery

In order to effectively treat fungal infections, current study aimed to increase the solubility of Econazole nitrate (EN) by use of solid dispersion (SD) technology and further integrate SD formulations of drug into hydrogel. Solvent evaporation method was used to develop SD formulations of EN with β-cyclodextrin and Soluplus® as carriers. The SD formulations were characterized for solubility determination, FTIR, DSC, XRD, drug content, and dissolution studies. Hydrogel formulations were evaluated for spreadability, viscosity, extrudability, drug activity, antifungal activity, in vitro permeation and skin irritation. The full conversion of EN from a crystalline to an amorphous state in solid dispersion was demonstrated by DSC and XRD studies. Compared with β-cyclodextrin, the SD formulation prepared with Soluplus® showed better solubility enhancement. Compared with pure drug formulation, SD formulation prepared with Soluplus® presented a 16-fold increase in drug solubility in a pH 5.5 solution. After that, hydrogel was mixed with free drug and optimised SD formulation. With a diameter of 5.5±0.7cm, EN-loaded SD-bearing hydrogel demonstrated good spreadability. Skin tolerability of EN was significantly improved by SD-based gel compared to plain gel, suggesting that it may be able to enhance topical administration and patient acceptance. EN containing Soluplus® solid dispersion gel displayed good adhesiveness and antifungal activity.