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

International Journal of Pharmaceutics

Volumn 441, Issue 1-2, 2013, Pages 323-333

  Devraj, Ravi ^a   Williams, Hywel D ^a   Warren, Dallas B ^a   Mullertz, Anette ^b   Porter, Christopher J H ^a   Pouton, Colin W ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Bile salt; Calcium; Lipid based drug delivery systems; Lipolysis; Pancreatic lipase; Poorly water soluble drugs

Indexed keywords

BILE SALT; CALCIUM; CALCIUM ION; DANAZOL; FATTY ACID; FENOFIBRATE; LIPID; SOAP; SOYBEAN OIL; TRIACYLGLYCEROL;

ANALYTIC METHOD; ARTICLE; COLLOID; DRUG DELIVERY SYSTEM; DRUG SOLUBILITY; DRUG STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO DIGESTION TESTING; MICELLE; PRECIPITATION; PRIORITY JOURNAL; SOLUBILIZATION;

BILE ACIDS AND SALTS; CALCIUM; CHEMICAL PRECIPITATION; COLLOIDS; DANAZOL; DIGESTION; DRUG DELIVERY SYSTEMS; FATTY ACIDS; FENOFIBRATE; LIPIDS; SOLUBILITY; SOYBEAN OIL; TRIGLYCERIDES;

EID: 84872796566     PISSN: 03785173     EISSN: 18733476     Source Type: Journal    
DOI: 10.1016/j.ijpharm.2012.11.024     Document Type: Article

References (76)

1. K. Ahmed, Y. Li, D.J. McClements, and H. Xiao Nanoemulsion- and emulsion-based delivery systems for curcumin: encapsulation and release properties Food Chem. 132 2012 799 807
2. F.J. Alvarez, and V.J. Stella The role of calcium ions and bile salts on the pancreatic lipase-catalyzed hydrolysis of triglyceride emulsions stabilized with lecithin Pharm. Res. 6 1989 449 457
3. M.U. Anby, H.D. Williams, M. McIntosh, H. Benameur, G.A. Edwards, C.W. Pouton, and C.J.H. Porter Lipid digestion as a trigger for supersaturation: evaluation of the impact of supersaturation stabilization on the in vitro and in vivo performance of self-emulsifying drug delivery systems Mol. Pharm. 9 2012 2063 2079
4. M. Armand, P. Borel, B. Pasquier, C. Dubois, M. Senft, M. Andre, J. Peyrot, J. Salducci, and D. Lairon Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum Am. J. Physiol. 271 1996 G172 G183
5. M. Armand, P. Borel, P. Ythier, G. Dutot, C. Melin, M. Senft, H. Lafont, and D. Lairon Effects of droplet size, triacylglycerol composition, and calcium on the hydrolysis of complex emulsions by pancreatic lipase an in vitro study J. Nutr. Biochem. 3 1992 333 341
6. J.C. Bakala N'Goma, S. Amara, K. Dridi, V. Jannin, and F. Carriere Understanding lipid digestion in the GI tract for effective drug delivery Ther. Deliv. 3 2012 105 124
7. V. Bakatselou, R.C. Oppenheim, and J.B. Dressman Solubilization and wetting effects of bile salts on the dissolution of steroids Pharm. Res. 8 1991 1461 1469
8. E. Bauer, S. Jakob, and R. Mosenthin Principles of physiology of lipid digestion Asian-Australas. J. Anim. Sci. 18 2005 282 295
9. S. Bernback, L. Blackberg, and O. Hernell The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase J. Clin. Invest. 85 1990 1221 1226
10. S. Bezzine, F. Ferrato, M.G. Ivanova, V. Lopez, R. Verger, and F. Carriere Human pancreatic lipase: colipase dependence and interfacial binding of lid domain mutants Biochemistry 38 1999 5499 5510
11. B. Borgstroem, G. Lundh, and A. Hofmann The site of absorption of conjugated bile salts in man Gastroenterology 45 1963 229 238
12. B. Borgstrom phosphatidylcholine as substrate for human pancreatic phospholipase-a(2)-importance of the physical state of the substrate Lipids 28 1993 371 375
13. B.J. Boyd, C.J. Porter, and W.N. Charman Using the polymer partitioning method to probe the thermodynamic activity of poorly water-soluble drugs solubilized in model lipid digestion products J. Pharm. Sci. 92 2003 1262 1271
14. H. Brockerhoff Substrate specificity of pancreatic lipase Biochim. Biophys. Acta 159 1968 296 303
15. H. Brockerhoff, and R.G. Jensen Kinetics of Lipolysis 1974
16. M.C. Carey, and D.M. Small Physical-chemistry of cholesterol solubility in bile-relationship to gallstone formation and dissolution in man J. Clin. Invest. 61 1978 998 1026
17. M.C. Carey, D.M. Small, and C.M. Bliss Lipid digestion and absorption Annu. Rev. Physiol. 45 1983 651 677
18. F. Carriere, J.A. Barrowman, R. Verger, and R. Laugier Secretion and contribution to lipolysis of gastric and pancreatic lipases during a test meal in humans Gastroenterology 105 1993 876 888
19. F. Carriere, E. Rogalska, C. Cudrey, F. Ferrato, R. Laugier, and R. Verger In vivo and in vitro studies on the stereoselective hydrolysis of tri- and diglycerides by gastric and pancreatic lipases Bioorg. Med. Chem. 5 1997 429 435
20. W.N. Charman, C.J. Porter, S. Mithani, and J.B. Dressman Physiochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH J. Pharm. Sci. 86 1997 269 282
21. W.N. Charman, M.C. Rogge, A.W. Boddy, and B.M. Berger Effect of food and a monoglyceride emulsion formulation on danazol bioavailability J. Clin. Pharmacol. 33 1993 381 386
22. J.O. Christensen, K. Schultz, B. Mollgaard, H.G. Kristensen, and A. Mullertz Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium- and long-chain triacylglycerols Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 23 2004 287 296
23. A. Christiansen, T. Backensfeld, and W. Weitschies Effects of non-ionic surfactants on in vitro triglyceride digestion and their susceptibility to digestion by pancreatic enzymes Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 41 2010 376 382
24. R.G. Crounse Human pharmacology of griseofulvin: the effect of fat intake on gastrointestinal absorption J. Invest. Dermatol. 37 1961 529 533
25. J.F. Cuine, W.N. Charman, C.W. Pouton, G.A. Edwards, and C.J.H. Porter Increasing the proportional content of surfactant (Cremophor EL) relative to lipid in self-emulsifying lipid-based formulations of danazol reduces oral bioavailability in beagle dogs Pharm. Res. 24 2007 748 757
26. J. de Caro, C. Eydoux, S. Cherif, R. Lebrun, Y. Gargouri, F. Carriere, and A. De Caro Occurrence of pancreatic lipase-related protein-2 in various species and its relationship with herbivore diet Comp. Biochem. Physiol. B-Biochem. Mol. Biol. 150 2008 1 9
27. C. Erlanson-Albertsson Pancreatic colipase-structural and physiological-aspects Biochim. Biophys. Acta 1125 1992 1 7
28. G. Fave, T.C. Coste, and M. Armand Physicochemical properties of lipids: new strategies to manage fatty acid bioavailability Cell. Mol. Biol. 50 2004 815 831
29. J.J. Gu, A.F. Hofmann, H.T. Ton-Nu, C.D. Schteingart, and K.J. Mysels Solubility of calcium salts of unconjugated and conjugated natural bile acids J. Lipid Res. 33 1992 635 646
30. S.F. Han, T.T. Yao, X.X. Zhang, L. Gan, C. Zhu, H.Z. Yu, and Y. Gan Lipid-based formulations to enhance oral bioavailability of the poorly water-soluble drug anethol trithione: effects of lipid composition and formulation Int. J. Pharm. 379 2009 18 24
31. D.J. Hauss Oral lipid-based formulations Adv. Drug Deliv. Rev. 59 2007 667 676
32. A.F. Hofmann The function of bile salts in fat absorption. The solvent properties of dilute micellar solutions of conjugated bile salts Biochem. J. 89 1963 57 68
33. 2+ ions J. Lipid Res. 33 1992 617 626
34. A.J. Humberstone, C.J. Porter, and W.N. Charman A physicochemical basis for the effect of food on the absolute oral bioavailability of halofantrine J. Pharm. Sci. 85 1996 525 529
35. S. Hwang, S. Lee, I.-S. Ahn, and J.-K. Jung Highly efficient production of monoglycerides by the continuous removal of fatty acids from lipase-catalyzed oil hydrolysis Biocatal. Biotransform. 27 2009 290 295
36. C.A. Jones, A.F. Hofmann, K.J. Mysels, and A. Roda The effect of calcium and sodium-ion concentration on the properties of dilute aqueous-solutions of glycine conjugated bile-salts-phase-behavior and solubility products of the calcium salts of the common glycine conjugated bile-acids J. Colloid Interface Sci. 114 1986 452 470
37. H. Kimura, Y. Futami, S. Tarui, and T. Shinomiya Activation of human pancreatic lipase activity by calcium and bile-salts J. Biochem. 92 1982 243 251
38. K. Kleberg, F. Jacobsen, D.G. Fatouros, and A. Mullertz Biorelevant media simulating fed state intestinal fluids: colloid phase characterization and impact on solubilization capacity J. Pharm. Sci. 99 2010 3522 3532
39. G.A. Kossena, W.N. Charman, B.J. Boyd, and C.J. Porter Influence of the intermediate digestion phases of common formulation lipids on the absorption of a poorly water-soluble drug J. Pharm. Sci. 94 2005 481 492
40. A. Larsen, R. Holm, M.L. Pedersen, and A. Mullertz Lipid-based formulations for danazol containing a digestible surfactant, Labrafil M2125CS: in vivo bioavailability and dynamic in vitro lipolysis Pharm. Res. 25 2008 2769 2777
41. A.T. Larsen, P. Sassene, and A. Müllertz In vitro lipolysis models as a tool for the characterization of oral lipid and surfactant based drug delivery systems Int. J. Pharm. 417 2011 245 255
42. Y. Li, M. Hu, and D.J. McClements Factors affecting lipase digestibility of emulsified lipids using an in vitro digestion model: proposal for a standardised pH-stat method Food Chem. 126 2011 498 505
43. A. Lindahl, A.L. Ungell, L. Knutson, and H. Lennernas Characterization of fluids from the stomach and proximal jejunum in men and women Pharm. Res. 14 1997 497 502
44. K.J. MacGregor, J.K. embelton, J.E. Lacy, E.A. Perry, L.J. Solomon, H. segger, and C.W. Pouton Influence of lipolysis on drug absorption from the gastrointestinal tract Adv. Drug Deliv. Rev. 25 1997 33 46
45. F.H. Mattson, and R.A. Volpenhein The digestion and absorption of triglycerides J. Biol. Chem. 239 1964 2772 2777
46. E.L. McConnell, H.M. Fadda, and A.W. Basit Gut instincts: explorations in intestinal physiology and drug delivery Int. J. Pharm. 364 2008 213 226
47. A. Munoz, J.P. Guichard, and P. Reginault Micronized fenofibrate Atherosclerosis 110 1994 S45 S48
48. J.S. Patton, P.A. Albertsson, C. Erlanson, and B. Borgstrom Binding of porcine pancreatic lipase and colipase in the absence of substrate studies by two-phase partition and affinity chromatography J. Biol. Chem. 253 1978 4195 4202
49. J.S. Patton, and M.C. Carey Watching fat digestion Science 204 1979 145 148
50. J.S. Patton, and M.C. Carey Inhibition of human pancreatic lipase-colipase activity by mixed bile salt-phospholipid micelles Am. J. Physiol. 241 1981 G328 G336
51. J.S. Patton, R.D. Vetter, B. Hamosh, B. Borgstroem, M.C. Lindstrom, and M.C. Carey The light microscopy of triglyceride digestion Food Microstruct. 4 1984 29 41
52. E.M. Persson, R.G. Nilsson, G.I. Hansson, L.J. Lofgren, F. Liback, L. Knutson, B. Abrahamsson, and H. Lennernas A clinical single-pass perfusion investigation of the dynamic in vivo secretory response to a dietary meal in human proximal small intestine Pharm. Res. 23 2006 742 751
53. C.J. Porter, A.M. Kaukonen, B.J. Boyd, G.A. Edwards, and W.N. Charman Susceptibility to lipase-mediated digestion reduces the oral bioavailability of danazol after administration as a medium-chain lipid-based microemulsion formulation Pharm. Res. 21 2004 1405 1412
54. C.J. Porter, C.W. Pouton, J.F. Cuine, and W.N. Charman Enhancing intestinal drug solubilisation using lipid-based delivery systems Adv. Drug Deliv. Rev. 60 2008 673 691
55. C.J. Porter, N.L. Trevaskis, and W.N. Charman Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs Nat. Rev. Drug Discov. 6 2007 231 248
56. C.J.H. Porter, M.U. Anby, D.B. Warren, H.D. Williams, H. Benameur, and C.W. Pouton Lipid based formulations: exploring the link between in vitro supersaturation and in vivo exposure Gattefosse Bull. 104 2011 61 69
57. C.W. Pouton Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and 'self-microemulsifying' drug delivery systems Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 11 Suppl. 2 2000 S93 S98
58. C.W. Pouton Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 29 2006 278 287
59. P.J. Sassene, M.M. Knopp, J.Z. Hesselkilde, V. Koradia, A. Larsen, T. Rades, and A. Mullertz Precipitation of a poorly soluble model drug during in vitro lipolysis: characterization and dissolution of the precipitate J. Pharm. Sci. 99 2010 4982 4991
60. T. Scherste Formation of lithogenic bile in man Digestion 9 1973 540 553
61. R.O. Scow, P. Desnuelle, and R. Verger Lipolysis and lipid movement in a membrane model. Action of lipoprotein lipase J. Biol. Chem. 254 1979 6456 6463
62. L. Sek, C.J. Porter, and W.N. Charman Characterisation and quantification of medium chain and long chain triglycerides and their in vitro digestion products, by HPTLC coupled with in situ densitometric analysis J. Pharm. Biomed. Anal. 25 2001 651 661
63. L. Sek, C.J. Porter, A.M. Kaukonen, and W.N. Charman Evaluation of the in-vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products J. Pharm. Pharmacol. 54 2002 29 41
64. M.T. Sheu, C.M. Yeh, and T.D. Sokoloski Characterization and dissolution of fenofibrate solid dispersion-systems Int. J. Pharm. 103 1994 137 146
65. V.H. Sunesen, R. Vedelsdal, H.G. Kristensen, L. Christrup, and A. Mullertz Effect of liquid volume and food intake on the absolute bioavailability of danazol, a poorly soluble drug Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 24 2005 297 303
66. A. Taillardat, A. Diederich, B. Sutter, O. Kalb, and J.F. Cuiné Use of in vitro dispersion and digestion tests to explain the in vivo performance of two lipid-based oral drug delivery systems in man Am. Pharm. Rev. 2007 10
67. A. Tan, A. Davey, and C. Prestidge Silica-Lipid Hybrid (SLH) versus non-lipid formulations for optimising the dose-dependent oral absorption of celecoxib Pharm. Res. 28 2011 2273 2287
68. N. Thomas, R. Holm, A. Mullertz, and T. Rades In vitro and in vivo performance of novel supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) J. Control. Release 160 2012 25 32
69. P.G. Welling Effects of food on drug absorption Annu. Rev. Nutr. 16 1996 383 415
70. T.F. Whayne, and J.M. Felts Activation of lipoprotein lipase-evaluation of calcium, magnesium, and ammonium as cofactors Circ. Res. 28 1971 649
71. M. Wickham, M. Garrood, J. Leney, P.D. Wilson, and A. Fillery-Travis Modification of a phospholipid stabilized emulsion interface by bile salt: effect on pancreatic lipase activity J. Lipid Res. 39 1998 623 632
72. H.D. Williams, P.J. Sassene, K. Kleberg, J.C. Bakala-N'Goma, M. Calderone, V. Jannin, A. Igonin, A. Partheil, D. Marchaud, E. Jule, J. Vertommen, M. Maio, R. Blundell, H. Benameur, F. Carrière, A. Müllertz, C.J.H. Porter, and C.W. Pouton Toward the establishment of standardized in vitro tests for lipid-based formulations, part 1: method parameterization and comparison of in vitro digestion profiles across a range of representative formulations J. Pharm. Sci. 103 2012 3360 3380
73. H.D. Williams, M.U. Anby, P.J. Sassene, K. Kleberg, J.C. Bakala-N'Goma, M. Calderone, V. Jannin, A. Igonin, A. Partheil, D. Marchaud, E. Jule, J. Vertommen, M. Maio, R. Blundell, H. Benameur, F. Carrière, A. Müllertz, C.W. Pouton, and C.J.H. Porter Toward the establishment of standardized in vitro tests for lipid-based formulations, part 2: the effect of bile salt concentration and drug loading on the performance of Type I, II, IIIA, IIIB and IV formulations during in vitro digestion Method parameterization and comparison of in vitro digestion profiles across a range of representative formulations 9 2012 3286 3300
74. H.D. Williams, N.L. Trevaskis, S.A. Charman, R.M. Shanker, W.N. Charman, C.W. Pouton, and C.J.H. Porter Strategies to address low drug solubility in discovery and development Pharmacol. Rev. 65 2013 1 185
75. N.H. Zangenberg, A. Mullertz, H.G. Kristensen, and L. Hovgaard A dynamic in vitro lipolysis model. I. Controlling the rate of lipolysis by continuous addition of calcium Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 14 2001 115 122
76. N.H. Zangenberg, A. Mullertz, H.G. Kristensen, and L. Hovgaard A dynamic in vitro lipolysis model. II: evaluation of the model Eur. J. Pharm. Sci.: Off. J. Eur. Fed. Pharm. Sci. 14 2001 237 244