Changed crystallinity of mebendazole solid dispersion: Improved anthelmintic activity

• Published in: International journal of pharmaceutics Vol. 403; no. 1-2; pp. 23 - 28
• Main Authors: García-Rodriguez, Juan J., de la Torre-Iglesias, Paloma M., Vegas-Sánchez, M. Carmen, Torrado-Durán, Susana, Bolás-Fernández, Francisco, Torrado-Santiago, Santiago
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17.01.2011; Elsevier
• Subjects: Animals; Anthelmintic activity; Antinematodal Agents - administration & dosage; Antinematodal Agents - chemistry; Antinematodal Agents - pharmacology; Antinematodal Agents - therapeutic use; Biological and medical sciences; Calorimetry, Differential Scanning; Cellulose - analogs & derivatives; Cellulose - chemistry; Chemistry, Pharmaceutical; crystal structure; Crystallization; differential scanning calorimetry; dispersions; Dissolution rate; Drug Carriers - chemistry; drugs; freeze drying; General pharmacology; in vivo studies; Mebendazole; Mebendazole - administration & dosage; Mebendazole - chemistry; Mebendazole - pharmacology; Mebendazole - therapeutic use; Medical sciences; Mice; Microscopy, Electron, Scanning; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Powder X-ray diffraction; scanning electron microscopy; Solid dispersions; Solubility; Surface Properties; Trichinella spiralis; Trichinella spiralis - drug effects; Trichinellosis - drug therapy; Trichinellosis - parasitology; X-Ray Diffraction; Mebendazole; Solid dispersions; Dissolution rate; Powder X-ray diffraction; Anthelmintic activity; Anthelmintic; Pharmaceutical technology; Solid dispersion; Crystallinity; X ray diffraction; Dissolution; Powder; Benzimidazole derivatives; Parasiticide
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2010.10.002

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.