Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium
Investigating the correlation between in vivo absorption and in vitro release of fenofibrate from lipid matrix particles in biorelevant medium
复制标题
DOI：
10.1016/j.ejps.2013.09.022
复制
发表时间：
2014-01-23
影响因子：
4.6
通讯作者：
Mu, Huiling
中科院分区：
文献类型：
--
作者：
Borkar, Nrupa;Xia, Dengning;Mu, Huiling
与液体脂质载体相比，脂质基质颗粒（LMP）可用作水溶性差的药物的更好载体，因为其在制剂中减少了药物动员。然而，固体脂质颗粒的消化过程及其对水溶性差的药物吸收的影响尚未完全了解。本研究旨在研究LMP粒径对药物体外释放和体内吸收的影响，以更好地了解脂质颗粒降解对药物溶解和吸收的影响。非诺贝特是一种水溶性差的模型药物，在这项研究中，使用探头超声处理被纳入LMP。所得LMP的特征在于粒径，粒径分布，zeta电位，包封率，体外脂解和在大鼠模型中的体内吸收。以高截留效率制备了三种不同粒径即约100 nm、400 nm和10 μ m（微粒）的LMP。体外脂解研究表明，在脂解30分钟后，100 nm和400 nm LMP在水相中的非诺贝特回收率显著高于微粒，表明纳米尺寸的LMP由于更大的比表面积而被更大程度地消化。100 nm LMP显示出更快的初始消化，然后是400 nm LMP和微粒。口服100 nm LMP后的血浆浓度时间曲线下面积（AUC）显著高于微粒和非诺贝特结晶混悬液（对照）（p < 0.01）。然而，在100 nm和400 nm LMP的AUC之间未观察到显著差异。观察到体内吸收和体外反应的等级顺序相同。非诺贝特在体外脂解过程中分配到水相中的回收率（%）和非诺贝酸的血药浓度-时间曲线的AUC的顺序为100 nm LMP >微粒>对照。总之，本研究证明了负载非诺贝特的LMP在大鼠模型中的生物利用度的粒度依赖性，其与在生物相关介质中进行的体外药物释放良好相关。(C)2013爱思唯尔有限公司版权所有。
Lipid matrix particles (LMP) may be used as better carriers for poorly water-soluble drugs than liquid lipid carriers because of reduced drug mobilization in the formulations. However, the digestion process of solid lipid particles and their effect on the absorption of poorly water-soluble drugs are not fully understood. This study aimed at investigating the effect of particle size of LMP on drug release in vitro as well as absorption in vivo in order to get a better understanding on the effect of degradation of lipid particles on drug solubilisation and absorption. Fenofibrate, a model poorly water-soluble drug, was incorporated into LMP in this study using probe ultrasound sonication. The resultant LMP were characterised in terms of particle size, size distribution, zeta potential, entrapment efficiency, in vitro lipolysis and in vivo absorption in rat model. LMP of three different particle sizes i.e. approximately 100 nm, 400 nm, and 10 mu m (microparticles) were produced with high entrapment efficiencies. The in vitro lipolysis study showed that the recovery of fenofibrate in the aqueous phase for 100 nm and 400 nm LMP was significantly higher (p < 0.05) than that of microparticles after 30 min of lipolysis, suggesting that nano-sized LMP were digested to a larger extent due to greater specific surface area. The 100 nm LMP showed faster initial digestion followed by 400 nm LMP and microparticles. The area under the plasma concentration time curve (AUC) following oral administration of 100 nm LMP was significantly higher (p < 0.01) than that of microparticles and fenofibrate crystalline suspension (control). However, no significant difference was observed between the AUCs of 100 nm and 400 nm LMP. The same rank order on the in vivo absorption and the in vitro response was observed. The recovery (%) of fenofibrate partitioning into the aqueous phase during in vitro lipolysis and the AUC of plasma concentration time curve of fenofibric acid was in the order of 100 nm LMP > microparticles > control. In summary, the present study demonstrated the particle size dependence of bioavailability of fenofibrate loaded LMP in rat model which correlates well with the in vitro drug release performed in the biorelevant medium. (C) 2013 Elsevier B.V. All rights reserved.