Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model
Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model
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DOI：
10.1016/j.ejps.2012.02.008
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发表时间：
2012-08-15
影响因子：
4.6
通讯作者：
Wasan, Kishor M.
中科院分区：
文献类型：
--
作者：
Ibrahim, Fady;Gershkovich, Pavel;Wasan, Kishor M.
本研究的目的是利用体外脂解模型研究新型口服两性霉素B脂基制剂的腔内加工。两性霉素B （AmB）由三种脂质成分组成：iCo-009、iCo-010和iCo-011。采用脂解模型消化不同的脂质负荷（0.25、0.5、1和2 g），以评估AmB在脂解相中的分布。除了2 g负载的iCo-009比iCo-010和iCo-011的脂肪分解时间明显更长外，三种配方的脂肪分解时间具有可比性。与其他制剂相比，iCo-009的脂质成分经历了较低程度的脂质分解。iCo-010水溶液中两性霉素B浓度最高，沉积物回收率最低。未消化脂质层中的两性霉素B水平在iCo-009和iCo-010之间具有可比性，且高于iCo-011。考虑到iCo-010在测试配方中具有最高的水胶束增溶性和最低的沉积物回收率，这些结果可能在未来的研究中用于解释和预测AmB- SEDDS配方的体内性能。爱思唯尔B.V.版权所有
The purpose of this study was to investigate the intraluminal processing of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Amphotericin B (AmB) was formulated in three lipid-based formulations consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various lipid loads (0.25, 0.5, 1 and 2 g) were digested using the lipolysis model to assess AmB distribution among the lipolysis phases. The duration of lipolysis was comparable among the three formulations except for 2 g load of iCo-009 which had a significantly longer lipolysis than iCo-010 and iCo-011. The lipid components of iCo-009 experienced lower extent of lipolysis as compared to other formulations. Amphotericin B concentration in the aqueous phases was the highest with iCo-010 which also had the lowest sediment recovery. Amphotericin B levels in the undigested lipid layers were comparable between iCo-009 and iCo-010 and were higher than with iCo-011. Given the observation that iCo-010 had the highest aqueous micellar solubilization and the lowest sediment recovery of AmB among the tested formulations, these results could potentially be used to interpret and predict the in vivo performance of AmB- SEDDS formulations in future studies. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.