Toward the establishment of standardized in vitro tests for lipid-based formulations. 5. Lipolysis of representative formulations by gastric lipase

Jean-Claude Bakala-N'Goma, Hywel David Williams, Philip Jonas Sassene, Karen Kleberg, Marilyn Calderone, Vincent Jannin, Annabel Igonin, Anette Partheil, Delphine Marchaud, Eduardo Jule, Jan Vertommen, Mario Maio, Ross Blundell, Hassan Benameur, Anette Mullertz, Colin William Pouton, Christopher John Porter, Frederic Carriere

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)

Abstract

Purpose: 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.
Original languageEnglish
Pages (from-to)1279-1287
Number of pages9
JournalPharmaceutical Research
Volume32
Issue number4
DOIs
Publication statusPublished - 2015

Keywords

  • digestion
  • drug delivery
  • lipid formulation
  • lipolysis
  • stomach

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