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伊曲康唑无定型固体分散体的制备及体外评价

洪子越, 施沈一, 郭玉申, 刘建平

洪子越, 施沈一, 郭玉申, 刘建平. 伊曲康唑无定型固体分散体的制备及体外评价[J]. 中国药科大学学报, 2018, 49(2): 187-194. DOI: 10.11665/j.issn.1000-5048.20180208
引用本文: 洪子越, 施沈一, 郭玉申, 刘建平. 伊曲康唑无定型固体分散体的制备及体外评价[J]. 中国药科大学学报, 2018, 49(2): 187-194. DOI: 10.11665/j.issn.1000-5048.20180208
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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
Citation: 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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伊曲康唑无定型固体分散体的制备及体外评价

  • 1.

    中国药科大学药剂系

  • 2.

    上海合全药业股份有限公司

Preparation of itraconazole amorphous solid dispersion and preliminary evaluation in vitro

摘要

    摘要
  • 摘要: 采用热熔挤出(HME)技术制备难溶性药物伊曲康唑(ITZ)无定型固体分散体并和原研药(RLD)作比较，为进一步的制剂研究提供基础。根据药物和载体的溶解度参数(δ)，玻璃态转化温度(Tg)，选择Soluplus，Kollidon VA64，HPMCAS和Eudragit EPO 4种载体。利用差示扫描量热法(MT-DSC)进行载体初步筛选，并运用HME技术成功制备基于这4种载体的伊曲康唑无定形固体分散体。通过MT-DSC、偏振光显微镜(PLM)、X射线衍射光谱(XRPD)和傅里叶变换红外光谱(FT-IR)对固体分散体的物理状态进行表征，探究药物与辅料的相互作用以及固体分散体的无定型状态。以体外溶出度和动力学溶解度为指标进一步考察4种载体及30%和50%两种载药量对体外溶出度的影响。结果显示，ITZ与Soluplus(3∶7)混合，在170 ℃下通过HME得到的固体分散体能显著提高溶出度，并且在40 ℃，75% 相对湿度条件下放置30 d未发生重结晶现象。MT-DSC等表征证实ITZ以无定型态与Soluplus达到分子层面互溶可能是其溶出度增加的主要因素。本研究为固体分散体的制备及理论研究提供了基础。
    Abstract: 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.
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    • 参考文献(15)
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  • 刊出日期:  2018-04-24

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