PURPOSE: For large scale preparation of stabilized itraconazole (ITZ) nanodispersions to improve the dissolution rate. METHOD: High-gravity technique was employed to produce ITZ nanodispersions. RESULTS: Stabilizer had a significant effect on the stability of drug nanoparticles. Hydroxypropylmethylcellulose was found to be the most effective stabilizer to prevent drug nanoparticles from aggregation. ITZ nanoparticles with an average size of 210 nm were obtained. Mannitol was the suitable carrier matrix for improving the flowability and the dissolution rate of ITZ nanodispersion. The effects of operating variables on the particle size distribution were investigated in detail. The stability of ITZ nanodispersions was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and in vitro dissolution studies. After 6 months storage, the nanodispersion showed unchanged particles size, morphology, crystal state, chemical structure, and dissolution. In vitro dissolution rate indicated that the nanodispersion could significantly enhance the dissolution rate when compared to the commercial available Sporanox capsules. The nanodispersion achieved 70% of drug dissolution in 10 min, whereas the Sporanox capsules only dissolved 20% during the same period. CONCLUSION: This study demonstrated that high-gravity technique is a promising method for large scale production of nanodispersions to enhance the dissolution rate of poorly water-soluble drugs.
PURPOSE: For large scale preparation of stabilized itraconazole (ITZ) nanodispersions to improve the dissolution rate. METHOD: High-gravity technique was employed to produce ITZ nanodispersions. RESULTS: Stabilizer had a significant effect on the stability of drug nanoparticles. Hydroxypropylmethylcellulose was found to be the most effective stabilizer to prevent drug nanoparticles from aggregation. ITZ nanoparticles with an average size of 210 nm were obtained. Mannitol was the suitable carrier matrix for improving the flowability and the dissolution rate of ITZ nanodispersion. The effects of operating variables on the particle size distribution were investigated in detail. The stability of ITZ nanodispersions was characterized by scanning electron microscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and in vitro dissolution studies. After 6 months storage, the nanodispersion showed unchanged particles size, morphology, crystal state, chemical structure, and dissolution. In vitro dissolution rate indicated that the nanodispersion could significantly enhance the dissolution rate when compared to the commercial available Sporanox capsules. The nanodispersion achieved 70% of drug dissolution in 10 min, whereas the Sporanox capsules only dissolved 20% during the same period. CONCLUSION: This study demonstrated that high-gravity technique is a promising method for large scale production of nanodispersions to enhance the dissolution rate of poorly water-soluble drugs.