Enhancing Solubility of a BCS Class II Drug- Itraconazole by Developing and Optimizing Solid Lipid Nanoparticles...

Itraconazole (ICZ) has been approved by the FDA to treat many fungal infections including, blastomycosis, histoplasmosis, and aspergillosis. ICZ can be also used as prophylaxis in the population who are at high risk for developing systemic fungal infections, such as HIV patients, and chemotherapy patients.

However, since ICZ is a BCS Class II drug that has low solubility and high permeability, leads to low oral bioavailability. In addition, the absorption of ICZ from commercial oral dosage forms is highly affected by food intake and pH.

The current study aimed to develop, optimize, and characterize ICZ-loaded solid lipid nanoparticles (ICZ-SLNs) using a Central Composite Design for improved solubility and extendedrelease profile.

ICZ-SLNs were optimized based on physicochemical characteristics. ICZ-SLNs were also evaluated for differential scanning calorimetry (DSC), in-vitro release, lyophilization, transmission electron microscopy (TEM), and physicochemical stability at refrigerated and room temperatures for three months.

The optimized ICZ-SLNs formulation showed particle size, polydispersity index, zeta potential, drug content, and entrapment efficiency of 335.6±8.0 nm, 0.25±0.02, -23.8±0.5 mV, 98.3±2.5%, and 99.5±1.5%, respectively. ICZ-SLN dispersions showed extended-release profiles for ICZ compared to the control solution over 24 h. The absence of the endothermic melting drug peak of the lyophilized formulation indicated that the drug was converted to its amorphous form inside the solid matrix. In addition, TEM studies showed spherical shape nanoparticles. Moreover, the optimized ICZ-SLN formulation was stable at both tested storage conditions.

The current ICZ formulation could exhibit improved oral bioavailability with better therapeutic outcomes during the treatment of systemic fungal infections.