Changed crystallinity of mebendazole solid dispersion: Improved anthelmintic activity

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• 作者：Juan J. Garcí ; a-Rodriguez ; Paloma M. de la Torre-Iglesias ; M. Carmen Vegas-Sá ; nchez ; Susana Torrado-Durá ; n ; Francisco Bolá ; s-Ferná ; ndez ; Santiago Torrado-Santiago
• 关键词：Mebendazole ; Solid dispersions ; Powder X-ray diffraction ; Dissolution rate ; Anthelmintic activity
• 刊名：International Journal of Pharmaceutics
• 出版年：2011
• 出版时间：17 January 2011
• 年：2011
• 卷：403
• 期：1-2
• 页码：23-28
• 全文大小：831 K

文摘

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.