Bioavailability of seocalcitol II:: Development and characterisation of self-microemulsifying drug delivery systems (SMEDDS) for oral administration containing medium and long chain triglycerides
Bioavailability of seocalcitol II:: Development and characterisation of self-microemulsifying drug delivery systems (SMEDDS) for oral administration containing medium and long chain triglycerides
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DOI：
10.1016/j.ejps.2006.02.005
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发表时间：
2006-06-01
影响因子：
4.6
通讯作者：
Pedersen, Gitte Pommergaard
中科院分区：
文献类型：
--
作者：
Grove, Mette;Mullertz, Anette;Pedersen, Gitte Pommergaard
通过构建三元相图，可以确定含有中链甘油三酯（MC-SMEDDS）和长链甘油三酯（LC-SMEDDS）的两种自微乳化给药体系（SMEDDS），脂质、表面活性剂和助表面活性剂的比例相同。SMEDDS由25%的脂质、48%的表面活性剂和27%的助表面活性剂组成，MC-SMEDDS：黏稠油、cremophor RH40、akoline MCM和LC-SMEDDS：芝麻油、cremophor RH40、核桃油。用水稀释后，这两种SMEDDS都得到了透明至淡蓝色的透明微乳，液滴尺寸为30 nm。以维生素D类似物皂荚骨糖醇为模型化合物，从生物利用度和化学稳定性方面评价了所开发的SMEDDS的工业实用性。MC-SMEDDS和LC-SMEDDS在大鼠体内的吸收和生物利用度分别约为45%和18%，这表明尽管脂质成分的性质不同，但两种制剂的体内行为相似。与简单MCT和LCT解决方案相比，使用SMEDDS没有改善生物利用度（22-24%）（Grove， M., Pedersen, g.p., Nielsen, j.l., Mullertz， A., 2005）。皂荚骨糖醇的生物利用度。1 .生物相关介质中的溶解度与大鼠口服生物利用度的关系——中长链甘油三酯的作用。j .制药。科学94,1830-1838.)。在加速条件下（40℃/75% RH）储存3个月后，MC-SMEDDS和LC-SMEDDS中seocalcitol的浓度下降了10-11%，而MCT和LCT的简单脂质溶液的降解率不到3%。在本研究中，与开发的SMEDDS相比，简单的脂质溶液似乎是更好的选择，因为它的生物利用度略高，并且藻骨糖醇的化学稳定性更好。(c) 2006 Elsevier B.V.版权所有
By constructing ternary phase diagrams it was possible to identify two self-microemulsifying drug delivery systems (SMEDDS) containing either medium chain triglycerides (MC-SMEDDS) or long chain triglycerides (LC-SMEDDS), with the same ratio between lipid, surfactant and co-surfactant. The SMEDDS ended up having a composition of 25% lipid, 48% surfactant and 27% co-surfactant, MC-SMEDDS: viscoleo, cremophor RH40, akoline MCM and LC-SMEDDS: sesame oil, cremophor RH40, peceol. Upon dilution with water both SMEDDS resulted in clear to bluish transparent microemulsions with a narrow droplet size of 30 nm. The industrial usefulness of the developed SMEDDS was evaluated with regard to bioavailability and chemical stability using the vitamin D analogue, seocalcitol, as model compound. The absorption and bioavailability of seocalcitol in rats were approximately 45% and 18%, respectively, from both the MC-SMEDDS and LC-SMEDDS indicating similar in vivo behavior of the two formulations, despite the difference in nature of lipid component. There was no improvement in bicavailability by the use of SMEDDS, compared to the bioavailability achieved from simple MCT and LCT solutions (22-24%) (Grove, M., Pedersen, G.P., Nielsen, J.L., Mullertz, A., 2005. Bioavailability of seocalcitol. I. Relating solubility in biorelevant media with oral bioavailability in rats-effect of medium and long chain triglycerides. J. Pharm. Sci. 94, 1830-1838.). After 3 months' storage at accelerated conditions (40 degrees C/75% RH), a decrease in concentration of seocalcitol of 10-11% was found in MC-SMEDDS and LC-SMEDDS compared with a degradation of less than 3% for the simple lipid solutions of MCT and LCT. In this study the simple lipid solutions seem to be a better choice compared with the developed SMEDDS due to a slightly higher bioavailability and a better chemical stability of seocalcitol. (c) 2006 Elsevier B.V. All rights reserved.