宋航, 高利芳, 付强, 王珏, 何仲贵. 以Soluplus为载体的固体分散体提高螺内酯体外溶出和物理稳定性J. 药学学报, 2019,54(1): 14-21. doi: 10.16438/j.0513-4870.2018-0958
引用本文: 宋航, 高利芳, 付强, 王珏, 何仲贵. 以Soluplus为载体的固体分散体提高螺内酯体外溶出和物理稳定性J. 药学学报, 2019,54(1): 14-21. doi: 10.16438/j.0513-4870.2018-0958
SONG Hang, GAO Li-fang, FU Qiang, WANG Jue, HE Zhong-gui. Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with SoluplusJ. Acta Pharmaceutica Sinica, 2019,54(1): 14-21. doi: 10.16438/j.0513-4870.2018-0958
Citation: SONG Hang, GAO Li-fang, FU Qiang, WANG Jue, HE Zhong-gui. Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with SoluplusJ. Acta Pharmaceutica Sinica, 2019,54(1): 14-21. doi: 10.16438/j.0513-4870.2018-0958

以Soluplus为载体的固体分散体提高螺内酯体外溶出和物理稳定性

Improvement of in vitro dissolution and physical stability for spironolactone solid dispersion formulated with Soluplus

  • 摘要: 螺内酯属于生物药剂学分类系统第Ⅱ类药物,溶解性差,口服生物利用度低。因此,本文采用溶剂法制备螺内酯固体分散体,以提高其水溶解性。基于体外溶出实验对螺内酯固体分散体进行处方优化;采用差示扫描量热法、X射线衍射法和傅里叶转换红外光谱法,确定药物在载体材料中的物理状态和药物与载体材料之间可能存在的相互作用;最后,通过影响因素试验,明确影响螺内酯固体分散体稳定性的关键因素。结果表明,在以Soluplus和HPMC-E5为载体的固体分散体中,药物均以无定型态存在,且药物与载体之间均存在氢键相互作用。因此,其体外溶出速度显著提高。影响因素试验表明,以Soluplus为载体的固体分散体,其物理稳定性优于以HPMC-E5为载体的固体分散体。因此,通过溶剂法制备螺内酯-Soluplus固体分散体可以提高其体外溶出速度和物理稳定性。

     

    Abstract: Spironolactone, a class Ⅱ drug of the biopharmaceutics classification system, has low oral bioavailability due to poor solubility. Spironolactone solid dispersions were prepared using the solvent method in order to improve its aqueous solubility. Optimization studies of spironolactone solid dispersions were performed using in vitro dissolution tests. Differential scanning calorimetry, X-ray diffraction and Fourier transform infrared were used to investigate the physical state of the drug in carrier materials and to detect the possible interactions between the drug and carrier materials in the solid dispersions. In addition, stress tests were employed to elucidate the key factors which have influence on the stability of the spironolactone solid dispersions. Results showed that spironolactone in the solid dispersions formulated with Soluplus and HPMC-E5 were both in amorphous state and the hydrogen bonds between the drug and carrier materials were formed in the solid dispersion. Therefore, the in vitro dissolution of spironolactone was also significantly enhanced. Stress tests demonstrated that the physical stability of spironolactone solid dispersions prepared with Soluplus was greatly improved compared to those formulated with HPMC-E5. Thus, spironolactone solid dispersion formulated with Soluplus using the solvent method could be used to improve the in vitro dissolution and stability of poorly soluble drugs.

     

/

返回文章
返回