Cherniakov Irina, Domb Abraham J, Hoffman Amnon
The Hebrew University of Jerusalem, Institute for Drug Research, School of Pharmacy, Faculty of Medicine , P.O.B 12065, Jerusalem 91120 , Israel +972 2 675 7667, +972 544 692 657 ;
Expert Opin Drug Deliv. 2015 Jul;12(7):1121-33. doi: 10.1517/17425247.2015.999038. Epub 2015 Jan 5.
Thirty percent of top marketed drugs in the USA and 70% of all new drug candidates are lipophilic and exhibit poor water solubility. With such physicochemical properties, the oral bioavailability of these compounds lacks dose proportionality, is very limited and extremely erratic. Different lipid-based formulations have been explored in the past few decades to improve the oral delivery of such compounds. In recent years, the most popular approach is their incorporation into self-emulsifying drug delivery systems (SEDDS), with particular emphasis on self-nano-emulsifying drug delivery systems (SNEDDS).
This review offers an updated overview of SNEDDS application from the biopharmaceutical point of view. The focus of this review deals with the potential of SNEDDS utilization to overcome absorption barriers following oral administration of lipophilic drugs. This includes a comprehensive description of the primary mechanisms by which lipids and lipophilic excipients, used to formulate SNEDDS, could affect drug absorption, bioavailability and disposition following oral administration.
The utilization of SNEDDS to augment the oral bioavailability of poorly water-soluble drugs goes beyond improvement in drug's solubility, as was initially presumed. In fact, SNEDDS have a potential to increase oral bioavailability by multi-concerted mechanisms such as reduced intra-enterocyte metabolism by CYP P450 enzymes, reduced P-glycoprotein (P-gp) efflux activity and hepatic first-pass metabolism bypass via lymphatic absorption. This unique biopharmaceutical point of view, presented in this review, contributes to the understanding of proper drug candidate selection and of the approach in SNEDDS formulation design.
在美国，30%的畅销药物以及70%的新药候选物具有亲脂性，且水溶性较差。基于这些物理化学性质，这些化合物的口服生物利用度缺乏剂量比例性，非常有限且极不稳定。在过去几十年中，人们探索了不同的脂质制剂来改善此类化合物的口服给药。近年来，最流行的方法是将它们纳入自乳化药物递送系统（SEDDS），尤其侧重于自纳米乳化药物递送系统（SNEDDS）。
本综述从生物药剂学角度提供了SNEDDS应用的最新概述。本综述的重点在于SNEDDS在口服亲脂性药物后克服吸收障碍方面的应用潜力。这包括对用于制备SNEDDS的脂质和亲脂性辅料可能影响口服给药后药物吸收、生物利用度和处置的主要机制的全面描述。
利用SNEDDS提高难溶性药物的口服生物利用度，其作用超出了最初所认为的改善药物溶解度的范畴。事实上，SNEDDS有可能通过多种协同机制提高口服生物利用度，例如减少细胞色素P450酶介导的肠内细胞代谢、降低P-糖蛋白（P-gp）外排活性以及通过淋巴吸收绕过肝脏首过代谢。本综述中提出的这种独特的生物药剂学观点，有助于理解合适的候选药物选择以及SNEDDS制剂设计方法。
