title: Toward the establishment of standardized in vitro tests for lipid-based formulations. 5. Lipolysis of representative formulations by gastric lipase.
abstract: OBJECTIVE
  Lipid-based formulations (LBF) are substrates for digestive lipases and digestion can significantly alter their properties and potential to support drug absorption. LBFs have been widely examined for their behaviour in the presence of pancreatic enzymes. Here, the impact of gastric lipase on the digestion of representative formulations from the Lipid Formulation Classification System has been investigated.
  
  
  METHODS
  The pHstat technique was used to measure the lipolysis by recombinant dog gastric lipase (rDGL) of eight LBFs containing either medium (MC) or long (LC) chain triglycerides and a range of surfactants, at various pH values [1.5 to 7] representative of gastric and small intestine contents under both fasting and fed conditions.
  
  
  RESULTS
  All LBFs were hydrolyzed by rDGL. The highest specific activities were measured at pH 4 with the type II and IIIA MC formulations that contained Tween®85 or Cremophor EL respectively. The maximum activity on LC formulations was recorded at pH 5 for the type IIIA-LC formulation. Direct measurement of LBF lipolysis using the pHstat, however, was limited by poor LC fatty acid ionization at low pH.
  
  
  CONCLUSIONS
  Since gastric lipase initiates lipid digestion in the stomach, remains active in the intestine and acts on all representative LBFs, its implementation in future standardized in vitro assays may be beneficial. At this stage, however, routine use remains technically challenging.
authors.affiliation: CNRS, Aix Marseille Université, UMR7282 Enzymologie Interfaciale et de Physiologie de la Lipolyse, 31 Chemin Joseph-Aiguier, 13402, Marseille cedex 20, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Bakala-N'Goma
authors.forename: Hywel D
authors.initials: HD
authors.lastname: Williams
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Sassene
authors.forename: Karen
authors.initials: K
authors.lastname: Kleberg
authors.forename: Marilyn
authors.initials: M
authors.lastname: Calderone
authors.forename: Vincent
authors.initials: V
authors.lastname: Jannin
authors.forename: Annabel
authors.initials: A
authors.lastname: Igonin
authors.forename: Anette
authors.initials: A
authors.lastname: Partheil
authors.forename: Delphine
authors.initials: D
authors.lastname: Marchaud
authors.forename: Eduardo
authors.initials: E
authors.lastname: Jule
authors.forename: Jan
authors.initials: J
authors.lastname: Vertommen
authors.forename: Mario
authors.initials: M
authors.lastname: Maio
authors.forename: Ross
authors.initials: R
authors.lastname: Blundell
authors.forename: Hassan
authors.initials: H
authors.lastname: Benameur
authors.forename: Anette
authors.initials: A
authors.lastname: Müllertz
authors.forename: Colin W
authors.initials: CW
authors.lastname: Pouton
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Porter
authors.forename: Frédéric
authors.initials: F
authors.lastname: Carrière
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards; D004063:Digestion; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008049:Lipase / Q000737:chemistry / Q000378:metabolism*; D008066:Lipolysis; D010194:Pancreatin / Q000737:chemistry / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins; D013270:Stomach / Q000201:enzymology*; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D011994:Recombinant Proteins; D014280:Triglycerides; D010194:Pancreatin; D008049:Lipase