title: Water-in-oil microemulsions containing medium-chain fatty acids/salts: formulation and intestinal absorption enhancement evaluation.
abstract: OBJECTIVE
  Water-in-oil (w/o) microemulsions have been developed which, in addition to non-ionic medium-chain glycerides, incorporate ionic lipids, primarily medium-chain fatty acids, such as caprylic (C8) capric (C10) and lauric (C12) acids and their corresponding sodium salts. The absorption enhancing activity of w/o microemulsions incorporating these lipids was evaluated in the rat using Calcein (MW = 623) a water-soluble and poorly absorbed marker molecule.
  
  
  METHODS
  Phase diagrams were constructed where C8/C10 or C12 fatty acids were treated as lipophilic surfactants and their sodium salts as hydrophilic ones. The anesthetised rat model was employed to evaluate Calcein absorption upon a single intraduodenal administration from a solution and the various w/o microemulsions.
  
  
  RESULTS
  A wide range of clear and transparent w/o microemulsions were obtained at ambient temperature either in liquid or solid form when a fixed blend of medium chain fatty acid/salt was titrated by a fixed ratio of the oil containing the oil-soluble mono- and diglycerides and deionized water or physiological saline. Upon intraduodenal administration in the anesthetised rat, the absorption of Calcein was improved from about 2% in aqueous solution up to about 37% in w/o microemulsions. Solid and liquid formulations were equally effective in improving bioavailability. The absorption enhancement activity of the fatty acids/salts followed the order C8 approximately C10 > C12. Absorption enhancement of Calcein was significantly reduced in the absence or presence of low levels of C8/C10 mono-/diglycerides.
  
  
  CONCLUSIONS
  These results further support the use of medium-chain glycerides and fatty acids/salts in microemulsion formulations to improve intestinal absorption of water-soluble compounds.
authors.affiliation: Drug Delivery Department, Pharmaceutical Technologies, Smith-Kline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Constantinides
authors.forename: G
authors.initials: G
authors.lastname: Welzel
authors.forename: H
authors.initials: H
authors.lastname: Ellens
authors.forename: P L
authors.initials: PL
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Sturgis
authors.forename: S H
authors.initials: SH
authors.lastname: Yiv
authors.forename: A B
authors.initials: AB
authors.lastname: Owen
mesh_terms: D000818:Animals; D002210:Caprylates / Q000737:chemistry / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003652:Decanoic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D005227:Fatty Acids / Q000737:chemistry* / Q000493:pharmacokinetics*; D005452:Fluoresceins / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007477:Ions; D007850:Lauric Acids / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012492:Salts / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D014867:Water / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002210:Caprylates; D003652:Decanoic Acids; D004655:Emulsions; D005227:Fatty Acids; D005452:Fluoresceins; D007477:Ions; D007850:Lauric Acids; D012492:Salts; D014867:Water; C030358:lauric acid; C024098:6-carboxyfluorescein; C031492:octanoic acid; C007740:fluorexon