秦凌浩 于 泓. 水溶性高分子材料对蛇床子素结晶的抑制作用J. 药学学报, 2010,45(12): 1559-1564.
引用本文: 秦凌浩 于 泓. 水溶性高分子材料对蛇床子素结晶的抑制作用J. 药学学报, 2010,45(12): 1559-1564.
QIN Ling-Gao, Xu- Hong. Effect of water-soluble polymers on the inhibition of osthole crystallizationJ. 药学学报, 2010,45(12): 1559-1564.
Citation: QIN Ling-Gao, Xu- Hong. Effect of water-soluble polymers on the inhibition of osthole crystallizationJ. 药学学报, 2010,45(12): 1559-1564.

水溶性高分子材料对蛇床子素结晶的抑制作用

Effect of water-soluble polymers on the inhibition of osthole crystallization

  • 摘要:

    本文分别研究了水溶性高分子甲基纤维素 (MC)、羟丙甲基纤维素 (HPMC)、羟丙基纤维素 (HPC-M)、泊洛沙姆 (F68) 和聚维酮 (PVP) 对蛇床子素 (OST) 结晶的抑制作用, 考察了高分子浓度和黏度对其的影响, 并通过测定不同时间点的药物浓度绘制蛇床子素的药物浓度-时间关系曲线图。结果表明, HPMC对药物结晶抑制作用最为明显, 在测定时间内 (8 h) 维持药物浓度水平是空白对照的1.61, 其次是PVPMC, 分别为1.541.45倍。药物的结晶过程符合一级动力学方程, 根据结晶曲线回归计算其结晶速率常数, 结果显示抑制药物晶体形成最显著的高分子材料为HPMC-60SH-4000HPMC-60SH-10000。与空白对照相比, 吸附高分子的蛇床子素在pH 1.2盐酸和pH 6.8磷酸盐缓冲液中的累积溶出量均大幅提高, 表明高分子材料不但可以抑制OST晶体生长而且可改善难溶性药物的溶出行为。

     

    Abstract:

    This paper is to study the inhibitory effect of water soluble polymers — methyl cellulose (MC), hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC-M), poloxamer (F68) and polyvidon (PVP) on osthole (OST) crystallization and investigate the impact of polymer concentration and viscosity on crystallization behavior.  Also, UV spectrophotometry method was used to determine the drug concentration at different time point to draw the OST concentration-time curve.  Results show that HPMC has the most significant inhibition effect on OST crystallization, and drug concentration level is 1.61 times higher than that in control solution within 8 h followed by PVP (1.54) and MC (1.45) respectively.  The kinetics of OST recrystallization can be described using first-order reaction, and the crystallization rate constants obtained by analyzing the regression equation indicate that HPMC-60SH-4000 and HPMC-60SH-10000 can greatly influence OST crystal formation.  The dissolution rate of drugs precipitated from water-soluble polymer solutions is faster compared with controls in pH 1.2 HCl and pH 6.8 phosphate buffers, which demonstrated that water-soluble polymers can not only change the behavior of drug crystallization but markedly improve the dissolution rate of water insoluble drugs.

     

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