Jubilant LifeSciences, D-12, Sector 59, Noida 201301, India.
Arch Pharm Res. 2011 Oct;34(10):1691-700. doi: 10.1007/s12272-011-1013-3. Epub 2011 Nov 12.
The present study was undertaken to develop and evaluate an oro-dispersible, sustained release tablet of metoclopramide HCl. The technology was comprised of developing sustained release microparticles, and compression of resultant microspheres into a fast dispersible tablet by direct compression. The microspheres of metoclopramide HCl were prepared by an emulsification-solvent evaporation method using ethylcellulose as the matrix polymer. The prepared microspheres were evaluated for morphology, particle size, entrapment efficiency, and in vitro drug release characteristics. Scanning electron microscopy demonstrated spherical particles with a mean diameter of 81.27 ± 5.87 μm and the drug encapsulation efficiency was found to be 70.15 ± 3.06%. The process and formulation variables such as rotation speed, polymer concentration, and drug concentration influenced the drug encapsulation efficiency and in vitro drug release. Optimized microspheres were compressed into tablets which were comprised of metoclopramide HCl microspheres, 53% (w/v) of D-mannitol granules, 7% (w/w) of Polyplasdone XL 10, and 0.5% (w/w) of calcium stearate. The tablets demonstrated a hardness of 59 ± 3 N, friability of 0.21% and disintegration time of 27 ± 3 sec. The formulations were subjected to stability studies as per ICH guidelines and were found to be stable after a 6 month study. In vivo experiments conducted in rats demonstrated that a constant level of metoclopramide HCl in plasma could be maintained for up to 20 h at a suitable concentration for antiemetic activity. An appropriate combination of excipients made it possible to obtain orally disintegrating sustained release tablets of metoclopramide HCl using simple and conventional techniques.
本研究旨在开发和评价盐酸甲氧氯普胺的口腔速释缓释片。该技术包括开发缓释微球，并通过直接压缩将所得微球压缩成快速分散的片剂。盐酸甲氧氯普胺的微球通过乳化-溶剂蒸发法用乙基纤维素作为基质聚合物制备。对制备的微球进行形态学、粒径、包封效率和体外药物释放特性的评价。扫描电子显微镜显示，平均粒径为 81.27 ± 5.87 μm 的球形颗粒，药物包封效率为 70.15 ± 3.06%。工艺和制剂变量，如转速、聚合物浓度和药物浓度，影响药物包封效率和体外药物释放。优化后的微球被压缩成片剂，片剂由盐酸甲氧氯普胺微球、53%（w/v）D-甘露醇颗粒、7%（w/w）共聚维酮 XL10 和 0.5%（w/w）硬脂酸钙组成。片剂的硬度为 59 ± 3 N，脆碎度为 0.21%，崩解时间为 27 ± 3 秒。按照 ICH 指南对制剂进行稳定性研究，发现经过 6 个月的研究后仍稳定。在大鼠体内实验中，证明盐酸甲氧氯普胺在血浆中的浓度可以在 20 小时内保持在适当的止吐活性浓度。适当的辅料组合使得使用简单常规技术获得盐酸甲氧氯普胺的口腔速释缓释片剂成为可能。
