Self-Solidifying and Self-Nanoemulsifying Drug Delivery System of Itraconazole

Abstract

Objective: To improve solubility, dissolution, and permeability of BCS class II drug Itraconazole (ITZ) using a self solidifying self nano emulsifying drug delivery system (SNEDDS). Method: The solubility of ITZ was assessed in oils, surfactants, co-surfactants, and buffers. Surfactants, co-surfactants, and combination of surfactants (S-comb) were selected on the basis of emulsification efficacy test. The ability to solidify self emulsifying mixture was assessed and solid SNEDDSS was developed and optimised. Finding: Solubility of ITZ was found maximum in 0.1N HCl (0.120  0.07mg/mL) followed by SGF (0.089  0.01mg/mL). Out of 20 oils screened, Peceol showed highest solubility. Among all surfactants and co-surfactants studied, Labrafil M 1944 CS (LM 1944) showed highest potential to solubilize ITZ (14.91 mg/g). The globule size of the optimised formulation was found to be 40.11 nm with PDI of 0.144. Zeta potential study revealed the stability of the SNEDDS. Drug content of solid SNEDDS of ITZ was found within the range of 98.11% to 102.51%, which was found in the acceptable limit. It was observed that ITZ solid SNEDDS (SSNEDDS) showed a promising improvement in the in vitro dissolution profile compared to the plain ITZ and marketed product in all three-dissolution media. Nearly 3-fold enhancement of permeability of ITZ was attributed by uniformly dispersed globules with nano size. Analytical characterization demonstrated that the drug and excipients are compatible with amorphous characteristics of the ITZ. Novelty: The developed self solidifying SNEDDS of ITZ showed enhanced solubility, dissolution, and permeability in comparison to the pure drugs (ITZ). Self solidifying SNEDDS would be a novel approach to overcome the limitations associated with liquid dosage forms. Keywords: Itraconazole; Solubility; Bioavailability; Self Nano Emulsifying Drug Delivery System (SNEDDS); Permeability