Characterization of solid dispersions of itraconazole and vitamin E TPGS prepared by microwave technology

Abstract

Background: This study describes the influence of microwave irradiation (MW) on the preparation and properties of solvent-free solid dispersions (SDs) employing vitamin E D-α-tocopheryl polyethylene glycol (TPGS) 1000 succinate, with itraconazole as a model drug. Materials and methods: Itraconazole is characterized by low aqueous solubility and vitamin E TPGS was chosen as the surfactant carrier for the formulation of MW solid dispersions in different ratios. Their physicochemical characteristics were investigated by means of powder x-ray diffraction (PXRD), differential scanning calorimetry (DSC), diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy and hot-stage microscopy. Comparison with the corresponding physical mixtures and the drug alone allowed the relationship between influence of the technological process on physicochemical and morphological properties of the systems to be examined. Results: PXRD data confirmed the absence of phase transitions in the solid state of the drug subjected to MW alone. On the other hand, an amorphous form of the drug was obtained in the solid dispersion with the highest content of carrier investigated (1:3 w/w). All the SDs showed an improvement in the solubility and dissolution profile of the drug, with the best results obtained in the case of the 1:3 w/w SD. This was related to an interaction between the drug and the carrier with a complex that formed due to favorable H bonds, as demonstrated by DRIFT analysis. Conclusion: It was demonstrated that the amorphization of the drug led to an increase in wettability and a significant improvement in bioavailability. Therefore, SDs obtained by MW technique using vitamin E TPGS as carrier provide a promising way to increase the dissolution rate and solubility of poorly bioavailable drugs.