Preparation of itraconazole amorphous solid dispersion and preliminary evaluation<i> in vitro</i>

HONG Ziyue; SHI Shenyi; GUO Yushen; LIU Jianping

doi:10.11665/j.issn.1000-5048.20180208

Journal of China Pharmaceutical University > 2018 > 49(2): 187-194. > DOI: 10.11665/j.issn.1000-5048.20180208

HONG Ziyue, SHI Shenyi, GUO Yushen, LIU Jianping. Preparation of itraconazole amorphous solid dispersion and preliminary evaluation in vitro[J]. Journal of China Pharmaceutical University, 2018, 49(2): 187-194. DOI: 10.11665/j.issn.1000-5048.20180208

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Preparation of itraconazole amorphous solid dispersion and preliminary evaluation in vitro

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Aimed at developing new formulation, amorphous solid dispersion of itraconazole was prepared via hot-melt extrusion technology and compared with sporanox for improving its dissolution. According to the solubility parameter and glass transition temperature, Soluplus, Kollidon VA64, HPMCAS and Eudragit EPO were used as carriers. After screening the carriers by modulated temperature-differential scanning calorimetry(MT-DSC), the amorphous solid dispersion was prepared successfully and characterized by MT-DSC, polarized light microscope(PLM), X-ray powder diffraction(XRPD)and Fourier Transform InfraRed(FT-IR). Results suggested that the amorphous form of ITZ solid dispersion and whether the interaction between polymer and ITZ was appeared. Using 30% and 50% drug loading, solid dispersion were tested by in vitro dissolution and kinetic solubility tests. When using Soluplus(3 ∶7)as carrier and extrusion temperature of 170 ℃, dissolution rate of itraconazole was improved significantly compared to Sporanox. In 40 ℃, 75% RH condition, itraconazole in the solid dispersion was amorphous for 30 d with no crystal observed. MT-DSC indicated the molecular level miscibility between Soluplus and amorphous itraconazole was probably the main cause of solubilization. The result from this research help understanding the solublization of amorphous itraconazole and future formulation development.
- hot-melt extrusion,
- amorphous solid dispersion,
- itraconazole,
- dissolution,
- Soluplus

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