Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model

详细信息	查看全文 | 推荐本文 |

• 作者：Fady Ibrahim^a ; ^{fady@mail.ubc.ca} ; Pavel Gershkovich^a ; Olena Sivak^a ; Ellen K. Wasan^a ; ^b ; Kishor M. Wasan^a
• 关键词：AmB ; amphotericin B ; BCS ; Biopharmaceutical Classification System ; VitE-TPGS ; d-Alpha-tocopherol ; DSPE-PEG-2000 ; polyethylene-glycol-succinate-distearoylphosphatidylamine polyethyleneglycol-2000 ; DMSO ; dimethyl sulfoxide ; HPLC ; high performance liquid chr
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2012
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：15 August, 2012
• 卷：46
• 期：5
• 页码：323-328
• 文件大小：590 K

摘要

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.