Preparation and characterization of Posaconazole as a Nano-micelles using d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)

Abstract

Posaconazole (POCZ) is a newly developed extended-spectrum triazole that belongs to BCS class II. In patients with a weakened immune system, POCZ has been shown to be effective as an antifungal treatment for invasive infections caused by Candida and Aspergillus species. The aim of this study is the formulation of POCZ nano-micelles by using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to increase the solubility of practically insoluble POCZ. In order to increase their apparent solubility in water, nano-micelles are made by combining macromolecules that self-assemble into ordered structures capable of entrapping hydrophobic drug molecules in the interior domain. Dispersed colloidal systems, of which Nano-micelles are a subset, are a large and diverse group. POCZ nano-micelles are made with TPGS and tween 80. Six formulations were prepared and analyzed their micelles size, polydispersity index (PDI), entrapment efficiency (EE), drug loadings (DL), saturation solubility, and in-vitro release. The drug-loaded nano-micelles of the Posaconazole formula coded (POCZ6) were characterized, and their properties were found to be: micelles size (95.6±4.9 nm), PDI (0.34±0.09), EE (94.3±1.69%), DL (10.3%), and best solubility factor (1144). All POCZ formula contained TPGS: tween80 at (1:5:3) ratio showed better solubility than the pure drug. An in-vitro release study was conducted, and the results showed that the chosen formula POCZ6 released the entire dose of drug in 70 minutes, compared to only 23% for pure drug.