College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Arch Pharm Res. 2011 Oct;34(10):1711-7. doi: 10.1007/s12272-011-1015-1. Epub 2011 Nov 12.
To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 μm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the C(max) and AUC(0→8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC(0→8h) and T(max) of nifedipine in CNDE increased markedly and the C(max) of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine.
为了开发具有生物利用度增强作用的长效硝苯地平口服制剂，采用喷雾干燥法制备了载硝苯地平乙醇溶液的硝苯地平干微丸（NDE），然后用 Eudragit 丙烯酸树脂对 NDE 进行包衣，得到包衣硝苯地平干微丸（CNDE）。评价了 NDE 和 CNDE 的物理特性和生物利用度，并与硝苯地平粉末进行了比较。NDE 和 CNDE 均为球形，几何平均直径分别约为 6.64 和 8.68-8.75μm。与硝苯地平粉末相比，NDE 在 pH1.2 模拟胃液和 pH6.8 模拟肠液中 60min 内溶解的硝苯地平量分别增加了约 7 倍和 40 倍。与 NDE 相比，CNDE 中硝苯地平在两种溶出介质中的释放均受到延缓。与单独口服硝苯地平粉末相比，口服 NDE 后，硝苯地平的 C(max)和 AUC(0→8h)分别增加了约 13 倍和 7 倍，Tmax 显著降低。与 NDE 相比，CNDE 中的 AUC(0→8h)和 T(max)显著增加，C(max)显著降低。结论：CNDE 可以降低初始突释血浆浓度，并通过增强生物利用度延长硝苯地平的血浆水平维持时间，可能是硝苯地平上市长效口服制剂的潜在替代品之一。
