TY - JOUR

T1 - Toward the Establishment of Standardized In Vitro Tests for Lipid-Based Formulations. 5. Lipolysis of Representative Formulations by Gastric Lipase

AU - Bakala-N'Goma, Jean-Claude

AU - Williams, Hywel D.

AU - Sassene, Philip J.

AU - Kleberg, Karen

AU - Calderone, Marilyn

AU - Jannin, Vincent

AU - Igonin, Annabel

AU - Partheil, Anette

AU - Marchaud, Delphine

AU - Jule, Eduardo

AU - Vertommen, Jan

AU - Maio, Mario

AU - Blundell, Ross

AU - Benameur, Hassan

AU - Müllertz, Anette

AU - Pouton, Colin W.

AU - Porter, Christopher J. H.

AU - Carriere, Frederic

PY - 2015/4

Y1 - 2015/4

N2 - PurposeLipid-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.MethodsThe 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.ResultsAll 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.ConclusionsSince 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.

AB - PurposeLipid-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.MethodsThe 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.ResultsAll 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.ConclusionsSince 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.

KW - digestion

KW - drug delivery

KW - lipid formulation

KW - lipolysis

KW - stomach

U2 - 10.1007/s11095-014-1532-y

DO - 10.1007/s11095-014-1532-y

M3 - Journal article

C2 - 25288015

VL - 32

SP - 1279

EP - 1287

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 4

ER -