Thin film freezing-template emulsion of itraconazole to improve the dissolution properties of poorly water-soluble drugs

Thin film freezing is a particle engineering technology for the production of nanostructured amorphous solid dispersions. In the present study, we investigated the use of thin film freezing technology in combination with template emulsion to improve the dissolution and wetting properties of a poorly water-soluble drug, itraconazole (ITZ). X-ray powder diffraction and differential scanning calorimetry proved that both the thin film freezing-template emulsion formulation and the thin film freezing-cosolvent formulation were substantially amorphous. Due to the use of template emulsion. the hydrophobic drug substance was encapsulated into the internal phase of the emulsion. As a result, the template emulsion formulation exhibited enhanced wetting properties as compared with the cosolvent formulation. The dissolution rate of ITZ from the template emulsion formulation was greater than that of the cosolvent formulation. The selection of polymeric excipients significantly affected the dissolution properties of template emulsion formulations. Hypromellose (HPMC) and povidone (PVP) with different viscosity grades were compared. Results showed that the high viscosity grade HPMC (Methocel E50) reduced the precipitation rate of ITZ after the acidic-to-neutral transition. Both the chemical structure and the viscosity may contribute to the precipitation inhibition effect in the dissolution testing. In summary, thin film freezing-template emulsion technology significantly enhanced the wetting and dissolution properties of poorly water-soluble drugs. The technology could subsequently be used to enhance the oral absorption of drugs in which the drug dissolution is the rate-limiting process of oral absorption.