Área Tecnología Farmacéutica, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Instituto de Química de Rosario, IQUIR-CONICET, Rosario 2000, Argentina.
J Pharm Sci. 2013 Mar;102(3):1016-23. doi: 10.1002/jps.23448. Epub 2013 Jan 9.
This work investigated the feasibility of developing benznidazole (BZL) tablets, allowing fast, reproducible, and complete drug dissolution, by compressing BZL-Polyethylene Glycol (PEG) 6000 physical mixtures (PMs) and solid dispersions (SDs). SDs were prepared by the solvent evaporation method at different drug:polymer ratios (w/w). BZL-PEG 6000 formulations were characterized by X-ray diffraction (XRD), scanning electron microscopy, and dissolution studies. The preparation of SD-based BZL tablets by the wet granulation method was carried out and the influence of pregelatinized starch (PS) and starch (S) on the disintegration time and drug dissolution rate was analyzed. SDs showed a significant improvement in the release profile of BZL as compared with the pure drug. As demonstrated by XRD, the crystalline character of BZL remained almost unaltered in both PMs and SDs. BZL release from the PEG 6000 tablets increased by the presence of PS instead S. Unexpectedly, the BZL release from tablets containing PMs was almost equal as compared with the BZL release from tablets containing SDs. In conclusion, the results suggest that PEG 6000 and PS are suitable additives for the development of BZL tablets with enhanced dissolution behavior through the preparation of ordinary PMs, instead the laborious SDs.
本工作研究了通过压缩苯硝唑（BZL）-聚乙二醇 6000（PEG 6000）物理混合物（PM）和固体分散体（SD）来开发具有快速、重现性和完全药物溶出度的 BZL 片剂的可行性。SD 通过不同的药物：聚合物比例（w/w）的溶剂蒸发法制备。BZL-PEG 6000 制剂通过 X 射线衍射（XRD）、扫描电子显微镜和溶解研究进行了表征。通过湿法制粒法制备了基于 SD 的 BZL 片剂，并分析了预胶化淀粉（PS）和淀粉（S）对崩解时间和药物溶出速率的影响。与纯药物相比，SD 显著改善了 BZL 的释放曲线。正如 XRD 所证明的，在 PM 和 SD 中，BZL 的结晶性质几乎没有改变。PS 的存在增加了 PEG 6000 片剂中 BZL 的释放，而 S 的存在则降低了 BZL 的释放。出乎意料的是，与含有 SD 的片剂相比，含有 PM 的片剂中 BZL 的释放几乎相等。总之，结果表明，PEG 6000 和 PS 是通过制备普通 PM 而不是繁琐的 SD 来开发具有增强溶出行为的 BZL 片剂的合适添加剂。
