Department of Parasitology, Complutense University, 28040 Madrid, Spain.
Int J Pharm. 2011 Jan 17;403(1-2):23-8. doi: 10.1016/j.ijpharm.2010.10.002. Epub 2010 Oct 8.
To improve the efficacy of mebendazole (MBZ), a poorly water-soluble drug, MBZ solid dispersions containing different proportions of low-substituted hydroxypropylcellulose (L-HPC) were prepared by lyophilization process. The physical characteristics of recrystallized MBZ, and solid dispersions (SD) at different MBZ:L-HPC proportions were investigated in terms of morphology (scanning electron microscopy, SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate. The in vivo performance was assessed by anthelmintic activity studies against enteral (pre-adult) stage of Trichinella spiralis in mice. The XRD, DSC and SEM revealed a characteristic decrease in crystallinity when increasing the L-HPC proportions in the solid dispersions. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with recrystallized drug. The considerable improvement in the dissolution rate of MBZ from solid dispersions was attributed to decreased drug crystallinity and altered surface morphology (major) and to the wetting effect of L-HPC (minor). The in vivo studies revealed that the anthelmintic effects of solid dispersions in mice were significantly increased in comparison with recrystallized MBZ (1.74-fold for SD-1:1, 3.20-fold for SD-1:2.5 and 3.80-fold for SD-1:5). These results have shown the suitability of MBZ:L-HPC solid dispersions for the treatment of enteral helmintic diseases at low doses.
为了提高苯并咪唑（MBZ）这种水溶性差的药物的疗效，我们通过冻干法制备了含有不同比例低取代羟丙基纤维素（L-HPC）的 MBZ 固体分散体。我们从形态学（扫描电子显微镜，SEM）、粉末 X 射线衍射（XRD）、差示扫描量热法（DSC）和溶解速率等方面，研究了再结晶 MBZ 和不同 MBZ:L-HPC 比例的固体分散体（SD）的物理特性。我们通过抗肠道（前期）阶段旋毛虫的驱虫活性研究来评估体内性能。XRD、DSC 和 SEM 表明，随着固体分散体中 L-HPC 比例的增加，结晶度会出现特征性下降。与再结晶药物相比，溶解研究表明溶解速率有明显提高。MBZ 从固体分散体中显著提高溶解速率的原因主要归因于药物结晶度的降低和表面形态的改变（主要），以及 L-HPC 的润湿作用（次要）。体内研究表明，与再结晶 MBZ 相比，固体分散体在小鼠体内的驱虫效果显著提高（SD-1:1 为 1.74 倍，SD-1:2.5 为 3.20 倍，SD-1:5 为 3.80 倍）。这些结果表明，MBZ:L-HPC 固体分散体适合低剂量治疗肠道蠕虫病。
