Department of Orthopedics, Shin Kong Wu Ho-Su Memorial Hospital, 95 Wenchang Road School of Pharmacy, College of Pharmacy, Taipei, Taiwan.
J Pharm Pharmacol. 2010 Dec;62(12):1685-96. doi: 10.1111/j.2042-7158.2010.01182.x. Epub 2010 Oct 5.
This study attempted to characterise the in-vitro release profiles of fenofibrate (FFB) from a self-microemulsifying drug-delivery system (SMEDDS) for optimising formulation factors and dissolution conditions for in-vivo absorption.
The study was conducted by profiling the release of FFB formulated with either a complete solution or a micronised dispersion system (MDS) in a SMEDDS composed of medium-chain triglyceride (MCT) oil and surfactant mixtures S(mix) of TPGS and Tweens at different ratios (K(m) =TPGS/Tweens), with and without adding water. Optimised FFB SMEDDS formulations were then selected for in-vivo bioavailability study.
The release rates of FFB from TPGS/Tween 20 systems were faster than those from TPGS/Tween 80 systems at the same K(m) value. In both systems, the release rates of FFB increased with a decrease in the K(m) value. Furthermore, both the release rates and the amounts of FFB from MDS in the water medium decreased with an increasing percentage of S(mix) added to both water contents. However, the release rates and amounts of FFB from MDSs increased with an increasing percentage of S(mix) in a 0.025 M sodium lauryl sulfate (SLS) solution. It was further illustrated that the release of FFB from SMEDDSs was complete within 30 min in both the 0.025 M SLS solution and water medium, but the release of FFB from Tricor® or MDSs was limited in water medium. An optimised FFB SMEDDS with either Tween 20(E5(20)) or Tween 80(E5(80)) and one MDS were selected for a pharmacokinetic study to compare with Tricor(®). The results demonstrated that the area under the receiver operating curve and C(max) values were in the order of Tricor(®) > E5(80)≅E5(20) > MDS and Tricor(®)≅E5(80) > E5(20) > MDS, respectively. Conclusions The absorption of drug carried by SMEDDS might not be enhanced as a result of the smaller volume of water taken with oral administration of SMEDDSs and the agitation rate of the gastrointestinal tract not being strong enough to efficiently promote the self-microemulsification process to facilitate the in-vivo dissolution rate.
本研究试图对非诺贝特（FFB）自微乳给药系统（SMEDDS）的体外释放特性进行描述，以优化制剂因素和溶解条件，从而提高体内吸收效果。
本研究通过在含有中链甘油三酯（MCT）油和聚氧乙烯氢化蓖麻油（TPGS）与聚山梨醇酯（Tween）混合物 S(mix)的 SMEDDS 中，分别对完全溶解体系和微粉化分散体系（MDS）中 FFB 的释放情况进行分析，考察不同的混合比（K(m) = TPGS/Tween）以及是否添加水对释放情况的影响。在此基础上，选择优化后的 FFB SMEDDS 制剂进行体内生物利用度研究。
在相同 K(m)值下，TPGS/Tween 20 体系中 FFB 的释放速率快于 TPGS/Tween 80 体系。在两个体系中，FFB 的释放速率均随 K(m)值的降低而加快。此外，在水介质中，随着 S(mix)添加量的增加，MDS 中 FFB 的释放量和释放速率均降低。然而，在 0.025 M 十二烷基硫酸钠（SLS）溶液中，随着 S(mix)添加量的增加，MDS 中 FFB 的释放速率和释放量均增加。结果进一步表明，FFB 从 SMEDDS 中的释放可在 30 min 内完成，无论是在 0.025 M SLS 溶液还是在水介质中，但在水介质中 Tricor®或 MDS 的释放是有限的。为了进行药代动力学研究，选择了一种优化的 FFB SMEDDS，其中含有 Tween 20（E5（20））或 Tween 80（E5（80））和一种 MDS，并与 Tricor(®)进行比较。结果表明，接受者操作特征曲线下面积和 C(max)值的顺序为 Tricor(®)>E5(80)≅E5(20)>MDS 和 Tricor(®)≅E5(80)>E5(20)>MDS。结论：由于口服 SMEDDS 所需的水体积较小，以及胃肠道的搅拌速度不足以有效促进自微乳化过程，从而提高体内溶解速率，SMEDDS 携带的药物的吸收可能不会增强。
