title: Self-nano-emulsifying drug delivery systems: an update of the biopharmaceutical aspects.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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 ; irasolodkin@gmail.com.
authors.forename: Irina
authors.initials: I
authors.lastname: Cherniakov
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
authors.forename: Amnon
authors.initials: A
authors.lastname: Hoffman
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D005079:Excipients; D008055:Lipids; D004364:Pharmaceutical Preparations; D014867:Water
keywords: P-gp efflux; intra-enterocyte metabolism; lymphatic delivery; oral bioavailability; poorly water-soluble drugs; self-emulsifying drug delivery systems; solubilization