Shen HaiRong, Zhong MingKang
Department of Pharmacy, Huashan Hospital, Fudan University, 12 Wulumuqi M. Road, Shanghai, 200040, China.
J Pharm Pharmacol. 2006 Sep;58(9):1183-91. doi: 10.1211/jpp.58.9.0004.
Atorvastatin is insoluble in aqueous solution and the bioavailability after oral administration is low. Self-microemulsifying drug delivery systems (SMEDDS) containing atorvastatin have been successfully prepared to improve its bioavailability. SMEDDS is a mixture of lipid, surfactant, and cosurfactant, which are emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Pseudo-ternary phase diagrams composed of various excipients were plotted. Droplet size, zeta-potential and long-term physical stability of the formulations were investigated. The release of atorvastatin from SMEDDS capsules was studied using the dialysis bag method in 0.1 M HCl and phosphate buffer (pH 7.4), compared with the release of atorvastatin from a conventional tablet. A pharmacokinetic study was performed in 6 beagle dogs after oral administration of 6 mg kg-1 atorvastatin. The bioavailability of atorvastatin SMEDDS capsules was significantly increased compared with that of the conventional tablet. SMEDDS capsules consisting of Labrafil, propylene glycol and Cremophor RH40 provided the greatest bioavailability. Our studies indicate that the use of SMEDDS for the delivery of atorvastatin can improve its bioavailability.
阿托伐他汀在水溶液中不溶，口服后的生物利用度较低。已成功制备了含阿托伐他汀的自微乳化药物递送系统（SMEDDS）以提高其生物利用度。SMEDDS是脂质、表面活性剂和助表面活性剂的混合物，在胃肠道温和的消化蠕动下于水性介质中乳化。绘制了由各种辅料组成的伪三元相图。研究了制剂的粒径、ζ电位和长期物理稳定性。使用透析袋法在0.1 M盐酸和磷酸盐缓冲液（pH 7.4）中研究了阿托伐他汀从SMEDDS胶囊中的释放情况，并与阿托伐他汀从常规片剂中的释放情况进行了比较。在6只比格犬口服6 mg kg-1阿托伐他汀后进行了药代动力学研究。与常规片剂相比，阿托伐他汀SMEDDS胶囊的生物利用度显著提高。由Labrafil、丙二醇和聚氧乙烯蓖麻油RH40组成的SMEDDS胶囊具有最高的生物利用度。我们的研究表明，使用SMEDDS递送阿托伐他汀可提高其生物利用度。
