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
CNRS, Aix Marseille Université, UMR7282 Enzymologie Interfaciale et de Physiologie de la Lipolyse, 31 Chemin Joseph-Aiguier, 13402, Marseille cedex 20, France.
Pharm Res. 2015 Apr;32(4):1279-87. doi: 10.1007/s11095-014-1532-y. Epub 2014 Oct 7.
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.
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.
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.
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.
基于脂质的制剂（LBF）是消化脂肪酶的作用底物，消化过程可显著改变其性质及支持药物吸收的潜力。LBF在胰酶存在情况下的行为已得到广泛研究。在此，研究了胃脂肪酶对脂质制剂分类系统中代表性制剂消化的影响。
采用pH计技术，在空腹和进食条件下，于代表胃和小肠内容物的不同pH值（1.5至7）下，测量重组犬胃脂肪酶（rDGL）对8种含有中链（MC）或长链（LC）甘油三酯及一系列表面活性剂的LBF的脂解作用。
所有LBF均被rDGL水解。在pH 4时，分别含有吐温85或聚氧乙烯蓖麻油的II型和IIIA型MC制剂的比活性最高。IIIA-LC型制剂在pH 5时对LC制剂的活性最高。然而，使用pH计直接测量LBF脂解受到低pH下LC脂肪酸离子化程度差的限制。
由于胃脂肪酶在胃中启动脂质消化，在肠道中仍保持活性并作用于所有代表性LBF，因此在未来标准化体外试验中应用胃脂肪酶可能有益。然而，现阶段常规使用在技术上仍具有挑战性。
