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Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption

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Abstract

Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to ‘pre-process’ lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.

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Abbreviations

AUC:

Area under the curve

CCK:

Cholecystokinin

DAG:

Diacylglycerol

DGL:

Dog Gastric Lipase

EMA:

European Medicines Agency

FDA:

United States Food and Drug Administration

FFA:

Free Fatty acid

HGF:

Human Gastric Fluid

HGL:

Human Gastric Lipase

LBF:

Lipid Based Formulations

LCFA:

Long chain fatty acid

LCT:

Long chain triacylglycerol

LFCS:

Lipid Formulation Classification System

MAG:

Monoacylglycerol

MCFA:

Medium chain fatty acid

MCT:

Medium chain triacylglycerol

MRI:

Magnetic resonance imaging

PEI:

Pancreatic exocrine insufficiency

PWSD:

Poorly water-soluble drugs

rDGL:

Recombinant Dog Gastric Lipase

RGE:

Rabbit Gastric Extract

SGF:

Simulated Gastric Fluid

TAG:

Triacylglycerol

SCFA:

Short chain fatty acid

References

  1. Fleisher D, Li C, Zhou Y, Pao L-H, Karim A. Drug, meal and formulation interactions influencing drug absorption after oral administration: clinical implications. Clin Pharmacokinet. 1999;36(3):233–54.

    Article  CAS  PubMed  Google Scholar 

  2. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev. 2013;65(1):315–499.

    Article  PubMed  CAS  Google Scholar 

  3. Charman WN, Porter CJH, Mithani S, Dressman JB. Physiochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. J Pharm Sci. 1997;86(3):269–82.

    Article  CAS  PubMed  Google Scholar 

  4. Koziolek M, Garbacz G, Neumann M, Weitschies W. Simulating the postprandial stomach: Physiological considerations for dissolution and release testing. Mol Pharm. 2013;10(5):1610–22.

    Article  CAS  PubMed  Google Scholar 

  5. Koziolek M, Grimm M, Garbacz G, Kühn JP, Weitschies W. Intragastric volume changes after intake of a high-caloric, high-fat standard breakfast in healthy human subjects investigated by MRI. Mol Pharm. 2014;11(5):1632–9.

    Article  CAS  PubMed  Google Scholar 

  6. Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov. 2007;6(3):231–48.

    Article  CAS  PubMed  Google Scholar 

  7. Bakala-N’Goma JC, Amara S, Dridi K, Jannin V, Carrière F. Understanding the lipid-digestion processes in the GI tract before designing lipid-based drug-delivery systems. Ther Deliv. 2012;3(1):105–24.

    Article  PubMed  CAS  Google Scholar 

  8. Feinle-Bisset C, Azpiroz F. Dietary lipids and functional gastrointestinal disorders. Am J Gastroenterol. 2013;108(5):737–47.

    Article  CAS  PubMed  Google Scholar 

  9. Gargouri Y, Moreau H, Verger R. Gastric lipases: biochemical and physiological studies. Biochim Biophys Acta. 1989;1006(3):255–71.

    Article  CAS  PubMed  Google Scholar 

  10. Bernbäck S, Bläckberg L, Hernell O. Fatty acids generated by gastric lipase promote human milk triacylglycerol digestion by pancreatic colipase-dependent lipase. Biochim Biophys Acta. 1989;1001(3):286–93.

    Article  PubMed  Google Scholar 

  11. Armand M. Lipases and lipolysis in the human digestive tract: where do we stand? Curr Opin Clin Nutr Metab Care. 2007;10(2):156–64.

    Article  CAS  PubMed  Google Scholar 

  12. Gargouri Y, Pieroni G, Rivière C, Lowe PA, Saunière JF, Sarda L, et al. Importance of human gastric lipase for intestinal lipolysis: an in vitro study. Biochim Biophys Acta. 1986;879(3):419–23.

    Article  CAS  PubMed  Google Scholar 

  13. Lemarié F, Cavalier J-F, Garcia C, Boissel F, Point V, Catheline D, et al. Effect of preduodenal lipase inhibition in suckling rats on dietary octanoic acid (C8:0) gastric absorption and plasma octanoylated ghrelin concentration. Biochim Biophys Acta. 2016;1861(9):1111–20.

    Article  PubMed  CAS  Google Scholar 

  14. Carrière F, Barrowman JA, Verger R, Laugier R. Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans. Gastroenterology. 1993;105(3):876–88.

    Article  PubMed  Google Scholar 

  15. Gargouri Y, Sarda L, Ferrato F, Verger R. Kinetic assay of human gastric lipase on short and long chain triacylglycerol emulsions. Gastroenterology. 1986:19–22.

  16. Pafumi Y, Lairon D, De La Porte PL, Juhel C, Storch J, Hamosh M, et al. Mechanisms of inhibition of triacylglycerol hydrolysis by human gastric lipase. J Biol Chem. 2002;277(31):28070–9.

    Article  CAS  PubMed  Google Scholar 

  17. Bourlieu C, Ménard O, De La Chevasnerie A, Sams L, Rousseau F, Madec MN, et al. The structure of infant formulas impacts their lipolysis, proteolysis and disintegration during in vitro gastric digestion. Food Chem. 2015;182:224–35.

    Article  CAS  PubMed  Google Scholar 

  18. De Oliveira SC, Bourlieu C, Ménard O, Bellanger A, Henry G, Rousseau F, et al. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis. Food Chem. 2016;211:171–9.

    Article  PubMed  CAS  Google Scholar 

  19. de Oliveira SC, Bellanger A, Olivia M, Pladys P, Le Gouar Y, Dirson E, et al. Impact of homogenization of pasteurized human milk on gastric digestion in the preterm infant: a randomized controlled trial. Clin Nutr ESPEN. 2017;20:1–11.

    Article  PubMed  Google Scholar 

  20. Moreau H, Bernadac A, Gargouri Y, Benkouka F, Laugier R, Verger R. Immunocytolocalization of human gastric lipase in chief cells of the fundic mucosa. Histochemistry. 1989;91(5):419–23.

    Article  CAS  PubMed  Google Scholar 

  21. Moreau H, Laugier R, Gargouri Y, Ferrato F, Verger R. Human preduodenal lipase is entirely of gastric fundic origin. Gastroenterology. 1988;95(5):1221–6.

    Article  CAS  PubMed  Google Scholar 

  22. Borovicka J, Schwizer W, Mettraux C, Kreiss C, Remy B, Asal K, et al. Regulation of gastric and pancreatic lipase secretion by CCK and cholinergic mechanisms in humans. Am J Phys. 1997;273(2 Pt 1):G374–80.

    CAS  Google Scholar 

  23. Sams L, Paume J, Giallo J, Carrière F. Relevant pH and lipase for in vitro models of gastric digestion. Food Funct. 2015;

  24. Armand M, Hamosh M, DiPalma JS, Gallagher J, Benjamin SB, Philpott JR, et al. Dietary fat modulates gastric lipase activity in healthy humans. Am J Clin Nutr. 1995;62(1):74–80.

    Article  CAS  PubMed  Google Scholar 

  25. Carrière F, Renou C, Lopez V, De Caro J, Ferrato F, Lengsfeld H, et al. The specific activities of human digestive lipases measured from the in vivo and in vitro lipolysis of test meals. Gastroenterology. 2000;119(4):949–60.

    Article  PubMed  Google Scholar 

  26. Carrière F, Renou C, Ransac S, Lopez V, De Caro J, Ferrato F, et al. Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers. Am J Physiol Gastrointest Liver Physiol. 2001;281(1):G16–28.

    Article  PubMed  Google Scholar 

  27. Carrière F, Grandval P, Renou C, Palomba A, Priéri F, Giallo J, et al. Quantitative study of digestive enzyme secretion and gastrointestinal lipolysis in chronic pancreatitis. Clin Gastroenterol Hepatol. 2005;3(1):28–38.

    Article  PubMed  Google Scholar 

  28. Armand M, Borel P, Dubois C, Senft M, Peyrot J, Salducci J, et al. Characterization of emulsions and lipolysis of dietary lipids in the human stomach. Am J Phys. 1994;266(3 Pt 1):G372–81.

    CAS  Google Scholar 

  29. Renou C, Carrière F, Ville E, Grandval P, Joubert-Collin M, Laugier R. Effects of lansoprazole on human gastric lipase secretion and intragastric lipolysis in healthy human volunteers. Digestion. 2001;63(4):207–13.

    Article  CAS  PubMed  Google Scholar 

  30. Capolino P, Guérin C, Paume J, Giallo J, Ballester J-M, Cavalier J-F, et al. In vitro gastrointestinal lipolysis: replacement of human digestive lipases by a combination of rabbit gastric and porcine pancreatic extracts. Food Dig. 2011;2(1–3):43–51.

    Article  CAS  Google Scholar 

  31. Carrière F, Rogalska E, Cudrey C, Ferrato F, Laugier R, Verger R. In vivo and in vitro studies on the stereoselective hydrolysis of tri- and diglycerides by gastric and pancreatic lipases. Bioorg Med Chem. 1997;5(2):429–35.

    Article  PubMed  Google Scholar 

  32. Mottram HR, Evershed RP. Elucidation of the composition of bovine milk fat triacylglycerols using high-performance liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry. J Chromatogr A. 2001;926(2):239–53.

    Article  CAS  PubMed  Google Scholar 

  33. Blasi F, Montesano D, De Angelis M, Maurizi A, Ventura F, Cossignani L, et al. Results of stereospecific analysis of triacylglycerol fraction from donkey, cow, ewe, goat and buffalo milk. J Food Compost Anal. 2008;21(1):1–7.

    Article  CAS  Google Scholar 

  34. Beisson F, Tiss A, Rivière C, Verger R. Methods for lipase detection and assay: a critical review. Eur J Lipid Sci Tech. 2000;102(2):133–53.

    Article  CAS  Google Scholar 

  35. Carrière F, Moreau H, Raphel V, Laugier R, Benicourt C, Junien JL, et al. Purification and biochemical characterization of dog gastric lipase. Eur J Biochem. 1991;202(1):75–83.

    Article  PubMed  Google Scholar 

  36. Rogalska E, Ransac S, Verger R. Lipases, stereoselectivity of lipases II. Stereoselective hydrolysis of triglycerides by gastric and pancreatic lipases. J Biol Chem. 1990;265(33):20271–6.

    CAS  PubMed  Google Scholar 

  37. Hunter JE. Studies on effects of dietary fatty acids as related to their position on triglycerides. Lipids. 2001;36(7):655–68.

    Article  CAS  PubMed  Google Scholar 

  38. Lindmark-Månsson H. Fatty acids in bovine milk fat. Food Nutr Res. 2008;52:1–3.

    Article  Google Scholar 

  39. Jensen RG. The composition of bovine milk lipids: January 1995 to December 2000. J Dairy Sci. 2002;85(2):295–350.

    Article  CAS  PubMed  Google Scholar 

  40. Roussel A, Canaan S, Egloff M-P, Rivière M, Dupuis L, Verger R, et al. Crystal structure of human gastric bipase and model of lysosomal acid lipase, two lipolytic enzymes of medical interest. J Biol Chem. 1999;274(24):16995–7002.

    Article  CAS  PubMed  Google Scholar 

  41. Roussel A, Miled N, Berti-Dupuis L, Rivière M, Spinelli S, Berna P, et al. Crystal structure of the open form of dog gastric lipase in complex with a phosphonate inhibitor. J Biol Chem. 2002;277(3):2266–74.

    Article  CAS  PubMed  Google Scholar 

  42. Bernbäck S, Bläckberg L. Human gastric lipase. The N-terminal tetrapeptide is essential for lipid binding and lipase activity. Eur J Biochem. 1989;182(3):495–9.

    Article  PubMed  Google Scholar 

  43. Sams L, Amara S, Chakroun A, Coudre S, Paume J, Giallo J, et al. Constitutive expression of human gastric lipase in Pichia pastoris and site-directed mutagenesis of key lid-stabilizing residues. Biochim Biophys Acta. 2017;1862(10):1025–34.

    Article  CAS  PubMed  Google Scholar 

  44. Chahinian H, Snabe T, Attias C, Fojan P, Petersen SB, Carrière F. How gastric lipase, an interfacial enzyme with a Ser-His-Asp catalytic triad, acts optimally at acidic pH. Biochemistry. 2006;45(3):993–1001.

    Article  CAS  PubMed  Google Scholar 

  45. Williams HD, Sassene P, Kleberg K, Bakala-N’Goma JC, Calderone M, Jannin V, et al. Establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range. J Pharm Sci. 2012;101(9):3360–80.

    Article  CAS  PubMed  Google Scholar 

  46. Ville E, Carrière F, Renou C, Laugier R. Physiological study of pH stability and sensitivity to pepsin of human gastric lipase. Digestion. 2002;5:73–81.

    Article  Google Scholar 

  47. Camacho-Ruiz MA, Mateos-Díaz JC, Carrière F, Rodriguez JA. A broad pH range indicator-based spectrophotometric assay for true lipases using tributyrin and tricaprylin. J Lipid Res. 2015;56(5):1057–67.

    Article  PubMed Central  CAS  Google Scholar 

  48. Gargouri Y, Pieroni G, Lowe PA, Sarda L, Verger R. Human gastric lipase. The effect of amphiphiles. Eur J Biochem. 1986;156:305–10.

    Article  CAS  PubMed  Google Scholar 

  49. FDA. Guidance for industry: food-effect bioavailability and fed bioequivalence studies 2002.

  50. Singh H, Gallier S. Nature’s complex emulsion: the fat globules of milk. Food Hydrocoll. 2017;68:81–9.

    Article  CAS  Google Scholar 

  51. Cortot A, Phillips SF, Malagelada JR. Gastric emptying of lipids after ingestion of a solid-liquid meal in humans. Gastroenterology. 1981;80(5 pt 1):922–7.

    CAS  PubMed  Google Scholar 

  52. Cortot A, Phillips SF, Malagelada JR. Gastric emptying of lipids after ingestion of an homogenized meal. Gastroenterology. 1979;76(5):939–44.

    CAS  PubMed  Google Scholar 

  53. Armand M, Pasquier B, André M, Borel P, Senft M, Peyrot J, et al. Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract. Am J Clin Nutr. 1999;70(6):1096–106.

    Article  CAS  PubMed  Google Scholar 

  54. Koziolek M, Schneider F, Grimm M, Modeβ C, Seekamp A, Roustom T, et al. Intragastric pH and pressure profiles after intake of the high-caloric, high-fat meal as used for food effect studies. J Control Release. 2015;220(Part A):71–8.

    Article  CAS  PubMed  Google Scholar 

  55. Golding M, Wooster TJ. The influence of emulsion structure and stability on lipid digestion. Curr Opin Colloid Interface Sci. 2010;15(1–2):90–101.

    Article  CAS  Google Scholar 

  56. Singh H, Ye A, Horne D. Structuring food emulsions in the gastrointestinal tract to modify lipid digestion. Prog Lipid Res. 2009;48(2):92–100.

    Article  CAS  PubMed  Google Scholar 

  57. Golding M, Wooster TJ, Day L, Xu M, Lundin L, Keogh J, et al. Impact of gastric structuring on the lipolysis of emulsified lipids. Soft Matter. 2011;7(7):3513.

    Article  CAS  Google Scholar 

  58. Schulze K. Imaging and modelling of digestion in the stomach and the duodenum. Neurogastroenterol Motil. 2006;18(3):172–83.

    Article  CAS  PubMed  Google Scholar 

  59. Ferrua MJ, Kong F, Singh RP. Computational modeling of gastric digestion and the role of food material properties. Trends Food Sci Technol. 2011;22(9):480–91.

    Article  CAS  Google Scholar 

  60. Ferrua MJ, Singh RP. Computational modelling of gastric digestion: current challenges and future directions. Curr Opin Food Sci. 2015;4:116–23.

    Article  Google Scholar 

  61. Hussein MO, Hoad CL, Wright J, Singh G, Stephenson MC, Cox EF, et al. Fat emulsion intragastric stability and droplet size modulate gastrointestinal responses and subsequent food intake in young adults 1 – 4. J Nutr. 2015:1–8.

  62. Marciani L, Wickham MSJ, Bush D, Faulks RM, Wright J, Fillery-Travis AJ, et al. Magnetic resonance imaging of the behaviour of oil-in-water emulsions in the gastric lumen of man. Br J Nutr. 2007;95(2):331.

    Article  CAS  Google Scholar 

  63. Weitschies W, Wilson CG. In vivo imaging of drug delivery systems in the gastrointestinal tract. Int J Pharm. 2011;417(1–2):216–26.

    Article  CAS  PubMed  Google Scholar 

  64. Dillard S, Krishnan S, Udaykumar HS. Mechanics of flow and mixing at antroduodenal junction. World J Gastroenterol. 2007;13(9):1365–71.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Boulby P, Moore R, Gowland PA, Spiller RC. Fat delays emptying but increases forward and backward antral flow as assessed by flow-sensitive magnetic resonance imaging. Neurogastroenterol Motil. 1999;11(1):27–36.

    Article  CAS  PubMed  Google Scholar 

  66. Hausken T, Li XN, Goldman B, Leotta D, Odegaard S, Martin RW. Quantification of gastric emptying and duodenogastric reflux stroke volumes using three-dimensional guided digital color Doppler imaging. Eur J Ultrasound. 2001;13(3):205–13.

    Article  CAS  PubMed  Google Scholar 

  67. Efentakis M, Dressman JB. Gastric juice as a dissolution medium: Surface tension and pH. Eur J Drug Metab Pharmacokinet. 1998;23(2):97–102.

    Article  CAS  PubMed  Google Scholar 

  68. Kalantzi L, Goumas K, Kalioras V, Abrahamsson B, Dressman JB, Reppas C. Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studies. Pharm Res. 2006;23(1):165–76.

    Article  CAS  PubMed  Google Scholar 

  69. Bergström CAS, Holm R, Jørgensen SA, Andersson SBE, Artursson P, Beato S, et al. Early pharmaceutical profiling to predict oral drug absorption: current status and unmet needs. Eur J Pharm Sci. 2014;57:173–99.

    Article  PubMed  CAS  Google Scholar 

  70. Vors C, Capolino P, Guérin C, Meugnier E, Pesenti S, Chauvin M-A, et al. Coupling in vitro gastrointestinal lipolysis and Caco-2 cell cultures for testing the absorption of different food emulsions. Food Funct. 2012;3(5):537.

    Article  CAS  PubMed  Google Scholar 

  71. Couëdelo L, Amara S, Lecomte M, Meugnier E, Monteil J, Fonseca L, et al. Impact of various emulsifiers on ALA bioavailability and chylomicron synthesis through changes in gastrointestinal lipolysis. Food Funct. 2015;6(5):1726–35.

    Article  PubMed  CAS  Google Scholar 

  72. Delorme V, Dhouib R, Canaan S, Fotiadu F, Carrière F, Cavalier JF. Effects of surfactants on lipase structure, activity, and inhibition. Pharm Res. 2011;28(8):1831–42.

    Article  CAS  PubMed  Google Scholar 

  73. Gargouri Y, Pieroni G, Ferrato F, Verger R. Human gastric lipase: a kinetic study with dicaprin monolayers. Eur J Biochem. 1987;169(1):125–9.

    Article  CAS  PubMed  Google Scholar 

  74. de La Fournière L, Ivanova MG, Blond JP, Carrière F, Verger R. Surface behaviour of human pancreatic and gastric lipases. Colloids Surf B Biointerfaces. 1994;2(6):585–93.

    Article  Google Scholar 

  75. Scheuble N, Lussi M, Geue T, Carrière F, Fischer P. Blocking gastric lipase adsorption and displacement processes with viscoelastic biopolymer adsorption layers. Biomacromolecules. 2016;17(10):3328–37.

    Article  CAS  PubMed  Google Scholar 

  76. Pasquier B, Armand M, Castelain C, Guillon F, Borel P, Lafont H, et al. Evaluation and lipolysis of triacylglycerols are altered by viscous soluble dietary fibres in acidic gastric medium in vitro. Biochem J. 1996;314:269–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Karhunen LJ, Juvonen KR, Huotari A, Purhonen AK, Herzig KH. Effect of protein, fat, carbohydrate and fibre on gastrointestinal peptide release in humans. Regul Pept. 2008;149(1–3):70–8.

    Article  CAS  PubMed  Google Scholar 

  78. Delzenne N, Blundell J, Brouns F, Cunningham K, De Graaf K, Erkner A, et al. Gastrointestinal targets of appetite regulation in humans: ILSI supplement. Obes Rev. 2010;11(3):234–50.

    Article  CAS  PubMed  Google Scholar 

  79. Camilleri M. Integrated upper gastrointestinal response to food intake. Gastroenterology. 2006;131(2):640–58.

    Article  CAS  PubMed  Google Scholar 

  80. Kwiatek MA, Menne D, Steingoetter A, Goetze O, Forras-Kaufman Z, Kaufman E, et al. Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI. Am J Physiol Gastrointest Liver Physiol. 2009;297(5):G894–901.

    Article  CAS  PubMed  Google Scholar 

  81. Goetze O, Steingoetter A, Menne D, van der Voort IR, Kwiatek MA, Boesiger P, et al. The effect of macronutrients on gastric volume responses and gastric emptying in humans: a magnetic resonance imaging study. Am J Physiol Gastrointest Liver Physiol. 2007;292(1):G11–7.

    Article  CAS  PubMed  Google Scholar 

  82. Doran S, Jones KL, Andrews JM, Horowitz M. Effects of meal volume and posture on gastric emptying of solids and appetite. Am J Physiol Regul Integr Comp Physiol. 1998;275(5):R1712–8.

    Article  CAS  Google Scholar 

  83. Hunt JN, Smith JL, Jiang CL. Effect of meal volume and energy density on the gastric emptying of carbohydrates. Gastroenterology. 1985;89(6):1326–30.

    Article  CAS  PubMed  Google Scholar 

  84. Calbet JA, MacLean DA. Role of caloric content on gastric emptying in humans. J Physiol. 1997;498(Pt 2):553–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Armand M, Borel P, Pasquier B, Dubois C, Senft M, André M, et al. Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum. Am J Phys. 1996;271(1 Pt 1):G172–83.

    CAS  Google Scholar 

  86. Yasui-Furukori N, Takahata T, Kondo T, Mihara K, Kaneko S, Tateishi T. Time effects of food intake on the pharmacokinetics and pharmacodynamics of quazepam. Br J Clin Pharmacol. 2003;55(4):382–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Saruwatari J, Yasui-Furukori N, Inoue Y, Kaneko S. Effect of dose timing in relation to food intake on systemic exposure to blonanserin. Eur J Clin Pharmacol. 2010;66(9):899–902.

    Article  CAS  PubMed  Google Scholar 

  88. Edelbroek M, Horowitz M, Maddox A, Bellen J. Gastric emptying and intragastric distribution of oil in the presence of a liquid or a solid meal. J Nucl Med. 1992;33(7):1283–90.

    CAS  PubMed  Google Scholar 

  89. Boulby P, Gowland P, Adams V, Spiller RC. Use of echo planar imaging to demonstrate the effect of posture on the intragastric distribution and emptying of an oil/water meal. Neurogastroenterol Motil. 1997;9(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  90. Marciani L, Faulks RM, Wickham MSJ, Bush D, Pick B, Wright J, et al. Effect of intragastric acid stability of fat emulsions on gastric emptying, plasma lipid profile and postprandial satiety. Br J Nutr. 2009;101(6):919–28.

    Article  CAS  PubMed  Google Scholar 

  91. Kunz P, Feinle-Bisset C, Faas H, Boesiger P, Fried M, Steingötter A, et al. Effect of ingestion order of the fat component of a solid meal on intragastric fat distribution and gastric emptying assessed by MRI. J Magn Reson Imaging. 2005;21(4):383–90.

    Article  PubMed  Google Scholar 

  92. Little TJ, Feinle-Bisset C. Effects of dietary fat on appetite and energy intake in health and obesity - oral and gastrointestinal sensory contributions. Physiol Behav. 2011;104(4):613–20.

    Article  CAS  PubMed  Google Scholar 

  93. Hildebrand P, Petrig C, Burckhardt B, Ketterer S, Lengsfeld H, Fleury A, et al. Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release. Gastroenterology. 1998;114(1):123–9.

    Article  CAS  PubMed  Google Scholar 

  94. Sundaresan S, Shahid R, Riehl TE, Chandra R, Nassir F, Stenson WF, et al. CD36-dependent signaling mediates fatty acid-induced gut release of secretin and cholecystokinin. FASEB J. 2013;27(3):1191–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Laugerette F, Passilly-Degrace P, Patris B, Niot I, Febbraio M, Montmayeur JP, et al. CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions. J Clin Invest. 2005;115(11):3177–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Feltrin KL, Little TJ, Meyer JH, Horowitz M, Smout AJPM, Wishart J, et al. Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length. Am J Physiol Gastrointest Liver Physiol. 2004;287(3):R524–33.

    CAS  Google Scholar 

  97. Little TJ, Russo A, Meyer JH, Horowitz M, Smyth DR, Bellon M, et al. Free fatty acids have more potent effects on gastric emptying, gut hormones, and appetite than triacylglycerides. Gastroenterology. 2007;133(4):1124–31.

    Article  CAS  PubMed  Google Scholar 

  98. McLaughlin J, Grazia Lucà M, Jones MN, D’Amato M, Dockray GJ, Thompson DG. Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility. Gastroenterology. 1999;116(1):46–53.

    Article  CAS  PubMed  Google Scholar 

  99. Fukumori R, Sugino T, Shingu H, Moriya N, Kobayashi H, Hasegawa Y, et al. Ingestion of medium chain fatty acids by lactating dairy cows increases concentrations of plasma ghrelin. Domest Anim Endocrinol. 2013;45(4):216–23.

    Article  CAS  PubMed  Google Scholar 

  100. Cummings DE, Shannon MH. Roles for ghrelin in the regulation of appetite and body weight. Arch Surg. 2003;138(4):389–96.

    Article  CAS  PubMed  Google Scholar 

  101. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–60.

    Article  CAS  PubMed  Google Scholar 

  102. Al Massadi O, Tschöp MH, Tong J. Ghrelin acylation and metabolic control. Peptides. 2011;32(11):2301–8.

    Article  PubMed  CAS  Google Scholar 

  103. Egelrud T, Ollvecrona T, Helander H. Studies on gastric absorption of lipids in the suckling rat. Scand J Gastroenterol. 1971;6(4):329–33.

    Article  CAS  PubMed  Google Scholar 

  104. Nishi Y, Hiejima H, Hosoda H, Kaiya H, Mori K, Fukue Y, et al. Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin. Endocrinology. 2005;146(5):2255–64.

    Article  CAS  PubMed  Google Scholar 

  105. Nishi Y, Mifune H. Chapter nineteen – ghrelin acylation by ingestion of medium-chain fatty acids. In: Methods in enzymology. 2012. p. 303–15.

  106. Hunt JN, Knox MT. A relation between the chain length of fatty acids and the slowing of gastric emptying. J Physiol. 1968;194(2):327–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. van Avesaat M, Troost FJ, Ripken D, Hendriks HF, Masclee AAM. Ileal brake activation: macronutrient specific effects on eating behavior? Int J Obes. 2014;(April):1–37.

  108. Van Citters GW, Lin HC. The ileal brake: a fifteen-year progress report. Curr Rep Gastroenterol. 1999;1(5):404–9.

    Article  Google Scholar 

  109. Cuche G, Cuber JC, Malbert CH. Ileal short-chain fatty acids inhibit gastric motility by a humoral pathway. Am J Physiol Gastrointest Liver Physiol. 2000;279(5):G925–30.

    Article  CAS  PubMed  Google Scholar 

  110. Hellström PM, Grybäck P, Jacobsson H. The physiology of gastric emptying. Best Pr Res Clin Anaesthesiol. 2006;20(3):397–407.

    Article  CAS  Google Scholar 

  111. Reppas C, Karatza E, Goumas C, Markopoulos C, Vertzoni M. Characterization of contents of distal ileum and cecum to which drugs/drug products are exposed during bioavailability/bioequivalence studies in healthy adults. Pharm Res. 2015;32(10):3338–49.

    Article  CAS  PubMed  Google Scholar 

  112. Dressman JB, Berardi RR, Dermentzoglou LC, Russell TL, Schmaltz SP, Barnett JL, et al. Upper gastrointestinal (GI) pH in young, healthy men and women. Pharm Res. 1990;7(7):756–61.

    Article  CAS  PubMed  Google Scholar 

  113. Simonian HP, Vo L, Doma S, Fisher RS, Parkman HP. Regional postprandial differences in pH within the stomach and gastroesophageal junction. Dig Dis Sci. 2005;50(12):2276–85.

    Article  PubMed  Google Scholar 

  114. Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology. 2008;134(7):1842–60.

    Article  CAS  PubMed  Google Scholar 

  115. Piper DW, Fenton BH. pH stability and activity curves of pepsin with special reference to their clinical importance. Gut. 1965;6(5):506–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Borovicka J, Schwizer W, Guttmann G, Hartmann D, Kosinski M, Wastiel C, et al. Role of lipase in the regulation of postprandial gastric acid secretion and emptying of fat in humans: a study with orlistat, a highly specific lipase inhibitor. Gut. 2000;46(6):774–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Degen L, Matzinger D, Drewe J, Nisslé S, Maecke H, Lengsfeld H, et al. Role of free fatty acids in regulating gastric emptying and gallbladder contraction. Digestion. 2007;74(3–4):131–9.

    Google Scholar 

  118. Dressman JB, Vertzoni M, Goumas K, Reppas C. Estimating drug solubility in the gastrointestinal tract. Adv Drug Deliv Rev. 2007;59(7):591–602.

    Article  CAS  PubMed  Google Scholar 

  119. Hörter D, Dressman JB. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev. 2001;46(1–3):75–87.

    Article  PubMed  Google Scholar 

  120. Feeney OM, Crum MF, McEvoy CL, Trevaskis NL, Williams HD, Pouton CW, et al. 50 years of oral lipid-based formulations: provenance, progress and future perspectives. Adv Drug Deliv Rev. 2016.

  121. Sahbaz Y, Williams HD, Nguyen TH, Saunders J, Ford L, Charman SA, et al. Transformation of poorly water-soluble drugs into lipophilic ionic liquids enhances oral drug exposure from lipid based formulations. Mol Pharm. 2015;12(6):1980–91.

    Article  CAS  PubMed  Google Scholar 

  122. Mu H, Holm R, Müllertz A. Lipid-based formulations for oral administration of poorly water-soluble drugs. Int J Pharm. 2013;453(1):215–24.

    Article  CAS  PubMed  Google Scholar 

  123. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and “self-microemulsifying” drug delivery systems. Eur J Pharm Sci. 2000;11(SUPPL 2):93–8.

    Article  Google Scholar 

  124. Pouton CW, Porter CJH. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Adv Drug Deliv Rev. 2008;60(6):625–37.

    Article  CAS  PubMed  Google Scholar 

  125. Bakala-N’Goma JC, Williams HD, Sassene P, Kleberg K, Calderone M, Jannin V, et al. Toward the establishment of standardized in vitro tests for lipid-based formulations. 5. Lipolysis of representative formulations by gastric lipase. Pharm Res. 2015;32(4):1279–87.

    Article  PubMed  CAS  Google Scholar 

  126. EMA. Guideline on the Investigation of Drug Interactions [Internet]. CPMP/EWP/560/95/Rev. 1 Corr.* Committee for Human Medicinal Products (CHMP); 2012.

  127. Carrière F. Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs. Biochimie. 2016;125:297–305.

    Article  PubMed  CAS  Google Scholar 

  128. Fernandez S, Jannin V, Rodier JD, Ritter N, Mahler B, Carrière F. Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters. Biochim Biophys Acta. 2007;1771(5):633–40.

    Article  CAS  PubMed  Google Scholar 

  129. Chatzidaki MD, Mateos-Diaz E, Leal-Calderon F, Xenakis A, Carrière F. Water-in-Oil microemulsions versus emulsions as carriers of hydroxytyrosol: an in vitro gastrointestinal lipolysis study using the pHstat technique. Food Funct. 2016;7:2258–69.

    Article  CAS  PubMed  Google Scholar 

  130. Kanicky JR, Shah DO. Effect of degree, type, and position of unsaturation on the pKa of long-chain fatty acids. J Colloid Interface Sci. 2002;256(1):201–7.

    Article  CAS  PubMed  Google Scholar 

  131. Egret-Charlier M, Sanson A, Ptak M, Bouloussa O. Ionization of fatty acids at the lipid - water inter face. FEBS Lett. 1978;89(2):313–6.

    Article  CAS  PubMed  Google Scholar 

  132. Kanicky JR, Shah DO. Effect of premicellar aggregation on the pKa of fatty acid soap solutions. Langmuir. 2003;19(6):2034–8.

    Article  CAS  Google Scholar 

  133. Cistola DP, Hamilton JA, Jackson D, Small DM. Ionization and phase behavior of fatty acids in water: application of the Gibbs phase rule. Biochemist. 1988;27(6):1881–8.

    Article  CAS  Google Scholar 

  134. Morigaki K, Walde P. Fatty acid vesicles. Curr Opin Colloid Interface Sci. 2007;12(2):75–80.

    Article  CAS  Google Scholar 

  135. Larsen AT, Sassene P, Müllertz A. In vitro lipolysis models as a tool for the characterization of oral lipid and surfactant based drug delivery systems. Int J Pharm. 2011;417(1–2):245–55.

    Article  CAS  PubMed  Google Scholar 

  136. Williams HD, Anby MU, Sassene P, Kleberg K, Bakala-N’Goma JC, Calderone M, et al. Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type. Mol Pharm. 2012;9(11):3286–300.

    Article  CAS  PubMed  Google Scholar 

  137. Devraj R, Williams HD, Warren DB, Müllertz A, Porter CJH, Pouton CW. In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products. Int J Pharm. 2013;441(1–2):323–33.

    Article  CAS  PubMed  Google Scholar 

  138. Li Y, Hu M, McClements DJ. Factors affecting lipase digestibility of emulsified lipids using an in vitro digestion model: proposal for a standardised pH-stat method. Food Chem. 2011;126(2):498–505.

    Article  CAS  Google Scholar 

  139. Christophersen PC, Christiansen ML, Holm R, Kristensen J, Jacobsen J, Abrahamsson B, et al. Fed and fasted state gastro-intestinal in vitro lipolysis: in vitro in vivo relations of a conventional tablet, a SNEDDS and a solidified SNEDDS. Eur J Pharm Sci. 2014;57:232–9.

    Article  CAS  PubMed  Google Scholar 

  140. McAllister M. Dynamic dissolution: a step closer to predictive dissolution testing? Mol Pharm. 2010;7(5):1374–87.

    Article  CAS  PubMed  Google Scholar 

  141. Koziolek M, Garbacz G, Neumann M, Weitschies W. Simulating the postprandial stomach: biorelevant test methods for the estimation of intragastric drug dissolution. Mol Pharm. 2013;10(6):2211–21.

    Article  CAS  PubMed  Google Scholar 

  142. Guerra A, Etienne-Mesmin L, Livrelli V, Denis S, Blanquet-Diot S, Alric M. Relevance and challenges in modeling human gastric and small intestinal digestion. Trends Biotechnol. 2012;30(11):591–600.

    Article  CAS  PubMed  Google Scholar 

  143. McClements DJ, Li Y. Review of in vitro digestion models for rapid screening of emulsion-based systems. Food Funct. 2010;1(1):32–59.

    Article  CAS  PubMed  Google Scholar 

  144. Baxevanis F, Kuiper J, Fotaki N. Fed-state gastric media and drug analysis techniques: current status and points to consider. Eur J Pharm Biopharm. 2016;107:234–48.

    Article  CAS  PubMed  Google Scholar 

  145. Klein S, Butler J, Hempenstall JM, Reppas C, Dressman JB. Media to simulate the postprandial stomach I. Matching the physicochemical characteristics of standard breakfasts. J Pharm Pharmacol. 2004;56(5):605–10.

    Article  CAS  PubMed  Google Scholar 

  146. Radwan A, Amidon GL, Langguth P. Mechanistic investigation of food effect on disintegration and dissolution of BCS class III compound solid formulations: the importance of viscosity. Biopharm Drug Dispos. 2012;33:403–16.

    Article  CAS  PubMed  Google Scholar 

  147. Radwan A, Ebert S, Amar A, Münnemann K, Wagner M, Amidon GL, et al. Mechanistic understanding of food effects: water diffusivity in gastrointestinal tract is an important parameter for the prediction of disintegration of solid oral dosage forms. Mol Pharm. 2013;10(6):2283–90.

    Article  CAS  PubMed  Google Scholar 

  148. van den Abeele J, Brouwers J, Mattheus R, Tack J, Augustijns P. Gastrointestinal behavior of weakly acidic BCS class II drugs in man - case study diclofenac potassium. J Pharm Sci. 2015;n/a-n/a.

  149. Diakidou A, Vertzoni M, Dressman JB, Reppas C. Estimation of intragastric drug solubility in the fed state: comparison of various media with data in aspirates. Biopharm Drug Dispos. 2009;30(6):318–25.

    Article  CAS  PubMed  Google Scholar 

  150. Macheras P, Koupparis M, Tsaprounis C. Drug dissolution studies in milk using the automated flow injection serial dynamic dialysis technique. Int J Pharm. 1986;33(1–3):125–36.

    Article  CAS  Google Scholar 

  151. Macheras PE, Koupparis MA, Antimisiaris SG. Effect of temperature and fat content on the solubility of hydrochlorothiazide and chlorothiazide in milk. J Pharm Sci. 1989;78(11):933–6.

    Article  CAS  PubMed  Google Scholar 

  152. Macheras PE, Koupparis MA, Antimisiaris SG. Drug binding and solubility in milk. Pharm Res. 1990;7(5):537–41.

    Article  CAS  PubMed  Google Scholar 

  153. Lopez C. Milk fat globules enveloped by their biological membrane: unique colloidal assemblies with a specific composition and structure. Curr Opin Colloid Interface Sci. 2011;16(5):391–404.

    Article  CAS  Google Scholar 

  154. Michalski MC. Specific molecular and colloidal structures of milk fat affecting lipolysis, absorption and postprandial lipemia. Eur J Lipid Sci Tech. 2009;111(5):413–31.

    Article  CAS  Google Scholar 

  155. Parodi PW. Positional distribution of fatty acids in triglycerides from milk of several species of mammals. Lipids. 1982;17(6):437–42.

    Article  CAS  PubMed  Google Scholar 

  156. Breckenridge WC, Kuksis A. Specific distribution of short-chain fatty acids in molecular distillates of bovine milk fat. J Lipid Res. 1968;9(3):388–93.

    CAS  PubMed  Google Scholar 

  157. Jantratid E, Janssen N, Reppas C, Dressman JB. Dissolution media simulating conditions in the proximal human gastrointestinal tract: an update. Pharm Res. 2008;25(7):1663–76.

    Article  CAS  PubMed  Google Scholar 

  158. Markopoulos C, Andreas CJ, Vertzoni M, Dressman JB, Reppas C. In-vitro simulation of luminal conditions for evaluation of performance of oral drug products: choosing the appropriate test media. Eur J Pharm Biopharm. 2015;93:173–82.

    Article  CAS  PubMed  Google Scholar 

  159. Kossena GA, Charman WN, Wilson CG, O’Mahony B, Lindsay B, Hempenstall JM, et al. Low dose lipid formulations: effects on gastric emptying and biliary secretion. Pharm Res. 2007;24(11):2084–96.

    Article  CAS  PubMed  Google Scholar 

  160. Charman WN, Rogge MC, Boddy AW, Berger BM. Effect of food and a monoglyceride emulsion formulation on danazol bioavailability. J Clin Pharmacol. 1993;33(4):381–6.

    Article  CAS  PubMed  Google Scholar 

  161. van Aken GA, Bomhof E, Zoet FD, Verbeek M, Oosterveld A. Differences in in vitro gastric behaviour between homogenized milk and emulsions stabilised by Tween 80, whey protein, or whey protein and caseinate. Food Hydrocoll. 2011;25(4):781–8.

    Article  CAS  Google Scholar 

  162. Moreau H, Abergel C, Carrière F, Ferrato F, Fontecilla-Camps JC, Cambillau C, et al. Isoform purification of gastric lipases. Towards crystallization. J Mol Biol. 1992;225(1):147–53.

    Article  CAS  PubMed  Google Scholar 

  163. Aoubala M, Douchet I, Laugier R, Hirn M, Verger R, De Caro A. Purification of human gastric lipase by immunoaffinity and quantification of this enzyme in the duodenal contents using a new ELISA procedure. Biochemistry. 1993;1169(2):183–8.

    CAS  Google Scholar 

  164. Moreau H, Gargouri Y, Lecat D, Junien JL, Verger R. Purification, characterization and kinetic properties of the rabbit gastric lipase. Biochim Biophys Acta. 1988;960:286–93.

    Article  CAS  PubMed  Google Scholar 

  165. Wicker-Planquart C, Canaan S, Rivière M, Dupuis L, Verger R. Expression in insect cells and purification of a catalytically active recombinant human gastric lipase. Protein Eng. 1996;9(12):1225–32.

    Article  CAS  PubMed  Google Scholar 

  166. Gruber V, Berna PP, Arnaud T, Bournat P, Clément C, Mison D, et al. Large-scale production of a therapeutic protein in transgenic tobacco plants: effect of subcellular targeting on quality of a recombinant dog gastric lipase. Mol Breed. 2001;7(4):329–40.

    Article  CAS  Google Scholar 

  167. Vardakou M, Sainsbury F, Rigby N, Mulholland F, Lomonossoff GP. Expression of active recombinant human gastric lipase in Nicotiana benthamiana using the CPMV-HT transient expression system. Protein Expr Purif. 2012;81(1):69–74.

    Article  CAS  PubMed  Google Scholar 

  168. Canaan S, Dupuis L, Rivière M, Faessel K, Romette JL, Verger R, et al. Purification and interfacial behavior of recombinant human gastric lipase produced from insect cells in a bioreactor. Protein Expr Purif. 1998;14(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  169. Bodmer MW, Angal S, Yarranton GT, Harris TJ, Lyons A, King DJ, et al. Molecular cloning of a human gastric lipase and expression of the enzyme in yeast. Biochim Biophys Acta. 1987;909(3):237–44.

    Article  CAS  PubMed  Google Scholar 

  170. Crabbe T, Weir AN, Walton EF, Brown ME, Sutton CW, Tretout N, et al. The secretion of active recombinant human gastric lipase by Saccharomyces cerevisiae. Protein Expr Purif. 1996;7(3):229–36.

    Article  CAS  PubMed  Google Scholar 

  171. Smerdon GR, Aves SJ, Walton EF. Production of human gastric lipase in the fission yeast Schizosaccharomyces pombe. Gene. 1995;165:313–8.

    Article  CAS  PubMed  Google Scholar 

  172. Sassene PJ, Fanø M, Mu H, Rades T, Aquistapace S, Schmitt B, et al. Comparison of lipases for in vitro models of gastric digestion: lipolysis using two infant formulas as model substrates. Food Funct. 2016;7(9):3989–98.

    Article  CAS  PubMed  Google Scholar 

  173. Aloulou A, Carrière F. Gastric lipase: an extremophilic interfacial enzyme with medical applications. Cell Mol Life Sci. 2008;65(6):851–4.

    Article  CAS  PubMed  Google Scholar 

  174. Zhong Q, Gu Z, Glatz CE. Extraction of recombinant dog gastric lipase from transgenic corn seed. J Agric Food Chem. 2006;54(21):8086–92.

    Article  CAS  PubMed  Google Scholar 

  175. Mercuri A, Passalacqua A, Wickham MSJ, Faulks RM, Craig DQ, Barker SA. The effect of composition and gastric conditions on the self-emulsification process of ibuprofen-loaded self-emulsifying drug delivery systems: a microscopic and dynamic gastric model study. Pharm Res. 2011;28(7):1540–51.

    Article  CAS  PubMed  Google Scholar 

  176. Diakidou A, Vertzoni M, Abrahamsson B, Dressman JB, Reppas C. Simulation of gastric lipolysis and prediction of felodipine release from a matrix tablet in the fed stomach. Eur J Pharm Sci. 2009;37(2):133–40.

    Article  CAS  PubMed  Google Scholar 

  177. Minekus M, Alminger M, Alvito P, Ballance S, Bohn T, Bourlieu C, et al. A standardised static in vitro digestion method suitable for food - an international consensus. Food Funct. 2014;5(6):1113–24.

    Article  CAS  PubMed  Google Scholar 

  178. Ghazal HS, Dyas AM, Ford JL, Hutcheon GA. The impact of food components on the intrinsic dissolution rate of ketoconazole. Drug Dev Ind Pharm. 2014:1–8.

  179. Luner PE, Van Der Kamp D. Wetting characteristics of media emulating gastric fluids. Int J Pharm. 2001;212(1):81–91.

    Article  CAS  PubMed  Google Scholar 

  180. Fernandez S, Chevrier S, Ritter N, Mahler B, Demarne F, Carrière F, et al. In vitro gastrointestinal lipolysis of four formulations of piroxicam and cinnarizine with the self emulsifying excipients Labrasol® and Gelucire® 44/14. Pharm Res. 2009;26(8):1901–10.

    Article  CAS  PubMed  Google Scholar 

  181. Abrahamsson B, Albery T, Eriksson A, Gustafsson I, Sjöberg M. Food effects on tablet disintegration. Eur J Pharm Sci. 2004;22(2–3):165–72.

    Article  CAS  PubMed  Google Scholar 

  182. Franek F, Holm P, Larsen F, Steffansen B. Interaction between fed gastric media (Ensure Plus®) and different hypromellose based caffeine controlled release tablets: comparison and mechanistic study of caffeine release in fed and fasted media versus water using the USP dissolution apparatus 3. Int J Pharm. 2014;461(1–2):419–26.

    Article  CAS  PubMed  Google Scholar 

  183. Williams HD, Nott KP, Barrett DA, Ward R, Hardy IJ, Melia CD. Drug release from HPMC matrices in milk and fat-rich emulsions. J Pharm Sci. 2011;100(11):4823–35.

    Article  CAS  PubMed  Google Scholar 

  184. Kalantzi L, Polentarutti B, Albery T, Laitmer D, Abrahamsson B, Dressman J, et al. The delayed dissolution of paracetamol products in the canine fed stomach can be predicted in vitro but it does not affect the onset of plasma levels. Int J Pharm. 2005;296(1–2):87–93.

    Article  CAS  PubMed  Google Scholar 

  185. Jain AK, Söderlind E, Viridén A, Schug B, Abrahamsson B, Knopke C, et al. The influence of hydroxypropyl methylcellulose (HPMC) molecular weight, concentration and effect of food on in vivo erosion behavior of HPMC matrix tablets. J Control Release. 2014;187:50–8.

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS AND DISCLOSURES

This work was supported by a fellowship within the Postdoc-Program of the German Academic Exchange Service (DAAD).

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Authors and Affiliations

  1. Department of Biopharmacy and Pharmaceutical Technology, Center of Drug Absorption and Transport, University of Greifswald, Germany, Felix-Hausdorff-Str. 3, D-17487, Greifswald, Germany

    Mirko Koziolek

  2. Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Mirko Koziolek & Christopher J. H. Porter

  3. Aix-Marseille Université, CNRS, UMR 7282 Enzymologie Interfaciale et de Physiologie de la Lipolyse, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20, France

    Frédéric Carrière

  4. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Christopher J. H. Porter

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  1. Mirko Koziolek
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Koziolek, M., Carrière, F. & Porter, C.J.H. Lipids in the Stomach – Implications for the Evaluation of Food Effects on Oral Drug Absorption. Pharm Res 35, 55 (2018). https://doi.org/10.1007/s11095-017-2289-x

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