Faculty of Pharmacy, The University of Sydney, NSW, Australia.
AAPS PharmSciTech. 2011 Dec;12(4):1431-41. doi: 10.1208/s12249-011-9709-8. Epub 2011 Oct 25.
The purpose of this work was to develop and optimize gliclazide-loaded alginate-methyl cellulose mucoadhesive microcapsules by ionotropic gelation using central composite design. The effect of formulation parameters like polymer blend ratio and cross-linker (CaCl(2)) concentration on properties of gliclazide-loaded alginate-methyl cellulose microcapsules like drug encapsulation efficiency and drug release were optimized. The optimized microcapsules were subjected to swelling, mucoadhesive, and in vivo studies. The observed responses coincided well with the predicted values from the optimization technique. The optimized microcapsules showed high drug encapsulation efficiency (83.57 ± 2.59% to 85.52 ± 3.07%) with low T(50%) (time for 50% drug release, 5.68 ± 0.09 to 5.83 ± 0.11 h). The in vitro drug release pattern from optimized microcapsules was found to be controlled-release pattern (zero order) with case II transport release mechanism. Particle sizes of these optimized microcapsules were 0.767 ± 0.085 to 0.937 ± 0.086 mm. These microcapsules also exhibited good mucoadhesive properties. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 12 h after oral administration of optimized mucoadhesive microcapsules. The developed and optimized alginate-methyl cellulose microcapsules are suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance.
本工作旨在通过离子凝胶化方法，使用中心复合设计开发和优化载格列齐特的海藻酸钠-甲基纤维素粘膜粘附微胶囊。考察了制剂参数（如聚合物混合比和交联剂（CaCl2）浓度）对载格列齐特的海藻酸钠-甲基纤维素微胶囊的性质（如药物包封效率和药物释放）的影响，并对其进行了优化。对优化后的微胶囊进行了溶胀、粘膜粘附和体内研究。观察到的响应与优化技术的预测值吻合良好。优化后的微胶囊表现出较高的药物包封效率（83.57±2.59%至 85.52±3.07%）和较低的 T（50%）（50%药物释放所需时间，5.68±0.09 至 5.83±0.11 h）。从优化后的微胶囊中观察到体外药物释放模式为控制释放模式（零级），具有 II 型传递释放机制。这些优化后的微胶囊的粒径为 0.767±0.085 至 0.937±0.086 mm。这些微胶囊还表现出良好的粘膜粘附性能。在链脲佐菌素诱导的糖尿病大鼠体内研究中，口服优化后的粘膜粘附微胶囊 12 h 后观察到显著的降血糖作用。开发和优化的海藻酸钠-甲基纤维素微胶囊适合于格列齐特的延长全身吸收，以维持较低的血糖水平并提高患者的顺应性。
