Kang Bok Ki, Lee Jin Soo, Chon Se Kang, Jeong Sang Young, Yuk Soon Hong, Khang Gilson, Lee Hai Bang, Cho Sun Hang
Department of Polymer Science and Engineering, Chonbuk National University, Duckjin Dong, Jeonju 561-756, South Korea.
Int J Pharm. 2004 Apr 15;274(1-2):65-73. doi: 10.1016/j.ijpharm.2003.12.028.
The main purpose of this work is to prepare self-microemulsifying drug delivery system (SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, simvastatin. Solubility of simvastatin was determined in various vehicles. SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal (GI) tract. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle size distributions of the resultant microemulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were Carpryol 90 (37%), Cremophor EL (28%), and Carbitol (28%). The release rate of simvastatin from SMEDDS was significantly higher than the conventional tablet. The prepared SMEDDS was compared with the conventional tablet (Zocor) by administering the prefilled hard capsules to fasted beagle dogs. The absorption of simvastatin acid from SMEDDS form resulted in about 1.5-fold increase in bioavailability compared with the conventional tablet. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as simvastatin by the oral route.
这项工作的主要目的是制备自微乳化药物递送系统（SMEDDS），以提高难溶性药物辛伐他汀的口服生物利用度。测定了辛伐他汀在各种载体中的溶解度。SMEDDS是油、表面活性剂和助表面活性剂的混合物，在胃肠道（GI）中温和搅拌和消化蠕动的条件下，在水性介质中乳化。构建了伪三元相图以确定有效的自乳化区域，并使用激光衍射粒度仪测定所得微乳液的粒度分布。用于体外溶出和生物利用度评估的优化配方为肉豆蔻酸异丙酯（37%）、聚氧乙烯蓖麻油EL（28%）和二甘醇单乙醚（28%）。辛伐他汀从SMEDDS中的释放速率显著高于传统片剂。通过给禁食的比格犬服用预填充硬胶囊，将制备的SMEDDS与传统片剂（舒降之）进行比较。与传统片剂相比，SMEDDS形式的辛伐他汀酸吸收导致生物利用度提高约1.5倍。我们的研究表明了SMEDDS在口服递送疏水性化合物（如辛伐他汀）方面的潜在用途。
