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  • ISSN 1006-3080
  • CN 31-1691/TQ

厄洛替尼固体分散体稳定化载体研究

宁尚琦 贾舒宇 景秋芳 任福正

宁尚琦, 贾舒宇, 景秋芳, 任福正. 厄洛替尼固体分散体稳定化载体研究[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20211111001
引用本文: 宁尚琦, 贾舒宇, 景秋芳, 任福正. 厄洛替尼固体分散体稳定化载体研究[J]. 华东理工大学学报(自然科学版). doi: 10.14135/j.cnki.1006-3080.20211111001
NING Shangqi, JIA Shuyu, JING Qiufang, REN Fuzheng. Stabilized Carriers of Erlotinib Amorphous Solid Dispersions[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20211111001
Citation: NING Shangqi, JIA Shuyu, JING Qiufang, REN Fuzheng. Stabilized Carriers of Erlotinib Amorphous Solid Dispersions[J]. Journal of East China University of Science and Technology. doi: 10.14135/j.cnki.1006-3080.20211111001

厄洛替尼固体分散体稳定化载体研究

doi: 10.14135/j.cnki.1006-3080.20211111001
基金项目: 上海市新药设计重点实验室项目(17DZ2271000)
详细信息
    作者简介:

    宁尚琦(1994—),女,黑龙江双鸭山市人,硕士生,主要研究方向:药物制剂。E-mail:sandyning_723@163.com

    通讯作者:

    任福正, E-mail:fzren@ecust.edu.cn

  • 中图分类号: R94

Stabilized Carriers of Erlotinib Amorphous Solid Dispersions

  • 摘要: 固体分散体(SDs)作为提高难溶性药物溶出度的主要技术之一,其能保持长期物理稳定性的关键是选择合适的载体。采用溶剂挥发法,选用六种聚合物为载体,制备厄洛替尼(ERL)SDs。通过Flory-Huggins相互作用参数χ与反溶剂显微观察评估了聚合物与ERL的相容性及对ERL结晶的影响,聚焦光束反射测量仪(FBRM)在线分析聚合物对结晶的过程调控作用机制。对不同比例SDs的固态性质进行表征,并测定了加速稳定性试验样品的无定型状态。结果表明,优选出的羟丙甲基纤维素能长期保持SDs中药物的无定型态,三种方法联合应用有助于快速选择最适载体。

     

  • 图  1  不同聚合物溶液中析出ERL晶体的显微照片(×100)

    Figure  1.  Microscope images (100×) of ERL in water without or with different polymers

    图  2  ERL峰面积对浓度线性回归的标准曲线

    Figure  2.  Standard curve of linear regression between peak area and concentration

    图  3  ERL在水中和聚合物溶液中粒子弦长随时间的变化曲线图

    Figure  3.  The variation curve of chord length of ERL microparticles in water and polymer aqueous solution

    图  4  不同质量比例ERL固体分散体的PXRD图

    Figure  4.  PXRD patterns of ERL SDs at different ratio (w/w)

    图  5  不同质量比例ERL固体分散体的DSC图 (a) ERL:聚合物=1:1; (b) ERL:聚合物=1:3.

    Figure  5.  DSC patterns of ERL SDs at different ratio (w/w) (a) ERL:Polymers=1:1; (b) ERL:Polymers=1:3.

    图  6  ERL-HPMC固体分散体红外光谱图(a) 4000~2000 cm−1和 (b) 2000~1000 cm−1.

    Figure  6.  FT-IR spectra of ERL-HPMC SDs (a) from 4000 to 2000 cm−1 and (b) 2000 to 1000 cm−1.

    图  7  ERL固体分散体在pH 6.8的PBS中的溶出曲线(n=6)

    Figure  7.  Dissolution profiles of ERL SDs in pH 6.8 phosphates buffer (n=6)

    图  8  ERL固体分散体稳定性试验典型PXRD图 (a) ERL-Soluplus; (b) ERL-羟丙甲基纤维素.

    Figure  8.  Typical PXRD patterns of ERL SDs stability test. (a) ERL- Soluplus; (b) ERL-HPMC.

    表  1  熔点降低法计算Flory-Huggins相互作用参数(χ)

    Table  1.   The Flory-Huggins interaction parameter (χ) calculated by melting point depression method

    ERL-Polymerχ
    ERL-Eud−0.175
    ERL-HPMCAS−0.249
    ERL-K30−0.756
    ERL-S630−0.853
    ERL-Soluplus−0.921
    ERL-HPMC−1.072
    下载: 导出CSV

    表  2  室温下ERL在聚合物溶液中的溶解度(n=3)

    Table  2.   The solubility of ERL in polymer solutions at room temperature (n=3)

    Solubility/(μg·mL−1)Standard deviation
    Water0.360.03
    HPMCAS0.550.05
    Eud0.430.04
    HPMC0.480.04
    S6300.560.03
    K300.530.07
    Soluplus21.760.18
    下载: 导出CSV

    表  3  加速稳定性试验样品中ERL的状态

    Table  3.   State of ERL in accelerated stability test sample

    ERL:PolymerTime(mon)EudHPMCASK30S630SoluplusHPMC
    3:11CCACCA
    2CCCCCC
    3CCCCCC
    6CCCCCC
    1:11CAAACA
    2CAAACA
    3CAAACA
    6CACCCA
    1:31AAAAAA
    2AAAACA
    3AAAACA
    6AAAACA
    *C: crystal; A: Amorphous
    下载: 导出CSV
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出版历程
  • 收稿日期:  2021-11-11
  • 网络出版日期:  2022-04-14

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