Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations. 5. Lipolysis of Representative Formulations by Gastric Lipase

• Published in: Pharmaceutical research Vol. 32; no. 4; pp. 1279 - 1287
• Main Authors: Bakala-N’Goma, Jean-Claude, Williams, Hywel D., Sassene, Philip J., Kleberg, Karen, Calderone, Marilyn, Jannin, Vincent, Igonin, Annabel, Partheil, Anette, Marchaud, Delphine, Jule, Eduardo, Vertommen, Jan, Maio, Mario, Blundell, Ross, Benameur, Hassan, Müllertz, Anette, Pouton, Colin W., Porter, Christopher J. H., Carrière, Frédéric
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.04.2015; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Chemistry, Pharmaceutical - methods; Chemistry, Pharmaceutical - standards; Digestion; Digestive system; Dogs; Drug delivery systems; Hydrogen-Ion Concentration; Hydrolysis; Lipase - chemistry; Lipase - metabolism; Lipids; Lipolysis; Medical Law; Pancreatin - chemistry; Pancreatin - metabolism; Pharmaceutical Preparations - chemistry; Pharmaceutical Preparations - metabolism; Pharmacology; Pharmacology/Toxicology; Pharmacy; Recombinant Proteins; Research Paper; Stomach; Stomach - enzymology; Triglycerides - chemistry; Triglycerides - metabolism; digestion; lipid formulation; stomach; drug delivery; lipolysis
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-014-1532-y

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.