Development of novel mucoadhesive pellets of metformin hydrochloride
Development of novel mucoadhesive pellets of metformin hydrochloride
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DOI：
10.1007/s12272-009-1312-0
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发表时间：
2009-03-01
影响因子：
6.7
通讯作者：
Kim, Jin-Seok
中科院分区：
文献类型：
--
作者：
Piao, Jingshu;Lee, Ji-Eun;Kim, Jin-Seok
使用离心流化（CF）造粒机通过粉末分层技术制备含有盐酸二甲双胍的粘膜粘附聚合物包衣微丸。使用四种高粘度聚合物来制造颗粒：1) 羟甲基纤维素 (HPMC)、2) 海藻酸钠 (Na-Alg)、3) HPMC/Carbopol 和 4) 羧甲基纤维素钠 (Na-CMC)。通过物理压碎试验、粘膜粘附试验、Zeta电位试验、体外释放研究和剂型胃滞留状态观察对微丸进行考察。通过粘膜粘附测试获得了Na-CMC包衣颗粒与粘蛋白盘之间的强粘附相互作用。在用于通过聚合物和粘蛋白颗粒之间的相互作用改变粘蛋白溶液的zeta电位值的聚合物中，Na-Alg是最有效的。药物溶出研究结果表明，四种微丸中超过 95% 的药物在 2 小时内释放，而 Na-CMC 和 Na-Alg 包衣微丸分别在 SGF（模拟胃液）和 SIF（模拟肠液）中表现出中等缓释。总之，Na-CMC 和 Na-Alg 似乎是粘膜粘附制剂的有希望的候选者，并且正在进一步研究以改善缓释特性，以实现盐酸二甲双胍每日一次制剂的最终目标。
Mucoadhesive polymer-coated pellets containing metformin hydrochloride were prepared by the powder-layering technique using a centrifugal fluidizing (CF)-granulator. Four high-viscosity polymers were applied to make the pellets: 1) hydroxymethylcellulose (HPMC), 2) sodium alginate (Na-Alg), 3) HPMC/Carbopol, and 4) sodium carboxylmethylcellulose (Na-CMC). The physical crushing test, mucoadhesive test, zeta-potential test, in vitro release study and observation of gastroretention state of the dosage form were performed to investigate the pellets. The strong adhesive interaction between the Na-CMC-coated pellets and the mucin disc was obtained by mucoadhesive test. Na-Alg was most effective among the polymers used in changing the value of zeta potential of the mucin solution by the interaction between a polymer and a mucin particle. Results from drug dissolution study showed that over 95% of the drug from all the four pellets was released before 2 h, while Na-CMC- and Na-Alg-coated pellets showed a moderate sustained-release in SGF (simulated gastric fluid) and SIF (simulated intestine fluid), respectively. In conclusion, Na-CMC and Na-Alg seem to be promising candidates for mucoadhesive formulation and further studies to improve the sustained-release property are underway for achieving the ultimate goal of once-a-day formulation of metformin hydrochloride.