Optimization and characterization of nimesulide bilayer tablets by response surface methodology

The objectives of this present investigation were to develop and formulate nimesulide bilayer tablets by using different polymer combinations and fillers, to optimize the formulations for different drug release variables by orthogonal design and central composite design-surface methodology and to evaluate drug release pattern of the optimized product. The bilayer tablet containing a fast release layer（FRL） and a sustained release layer（SRL） provided an initial burst release of nimesulide, followed by the sustained release for a period of time. The optimal formulation obtained was as follows：（I） the formulation of FRL： nimesulide, 50 mg; lactose, 92 mg; starch, 22 mg; CCMC-Na, 14 mg; PVP K30, 1 mg; micronized silica gel, 1 mg; magnesium stearate, 0.9 mg; and iron oxide red, 0.1 mg; and（II） the formulation of SRL： nimesulide, 150 mg; HPMC K100LV, 26 mg; HPMC K4M, 33 mg; lactose, 54 mg; PVP K30, 1 mg; micronized silica gel, 1 mg; and magnesium stearate, 0.9 mg. According to the optimal formulation, the biphasic type of release was identified. The in vitro drug dissolution from the bilayer tablets was sustained for about 16 h after releasing 15% of drug in the first 10 min. The developed nimesulide bilayer tablets with improved efficacy can perform therapeutically better than the conventional tablets.

咖啡酸苯乙酯纳米混悬剂的制备及其体外抑制乳腺癌细胞作用研究

目的优化咖啡酸苯乙酯纳米混悬剂的处方,并考察其体外抑制乳腺癌细胞作用。方法以泊洛沙姆188、蜂胶作为载体,采用反溶剂沉淀法制备,通过星点设计–效应面法优化最佳制备工艺参数,并考察咖啡酸苯乙酯纳米混悬剂的稳定性、载药量、包封率以及冻干保护剂的筛选,同时考察对4T1乳腺癌细胞的生长抑制作用和细胞摄取情况。结果咖啡酸苯乙酯纳米混悬剂的最优处方为蜂胶0.88 mg/mL、咖啡酸苯乙酯1.86 mg/mL、泊洛沙姆1881 mg/mL,制备得到咖啡酸苯乙酯纳米混悬剂平均粒径为150 nm左右,包封率98%以上,在各种生理介质中都能够稳定存在;0.5%的BSA对于咖啡酸苯乙酯纳米混悬剂的冻干保护效果最好。咖啡酸苯乙酯纳米混悬剂对4T1乳腺癌细胞的抑制作用与咖啡酸苯乙酯相比提高了2.95倍。咖啡酸苯乙酯纳米混悬剂被细胞摄取后主要分布在细胞质中,随着给药时间的增长,摄取也逐步提高。结论所得咖啡酸苯乙酯纳米混悬剂具有较高的包封率、载药量,并显著提高了咖啡酸苯乙酯对于4T1细胞的抑制作用。