In vitro digestion of the self-emulsifying lipid excipient labrasol ® by gastrointestinal lipases and influence of its colloidal structure on lipolysis rate

Pharmaceutical Research

Volumn 30, Issue 12, 2013, Pages 3077-3087

  Fernandez, Sylvie ^a,b   Jannin, Vincent ^b   Chevrier, Stéphanie ^b   Chavant, Yann ^b   Demarne, Frédéric ^b   Carrière, Frédéric ^a  

^a Centre National de la Recherche Scientifique   (France)

^b GATTEFOSSÉ SAS   (France)

Author keywords

carboxyl ester hydrolase; enzyme; gastric lipase; gastrointestinal lipolysis; macrogolglycerides; oral drug delivery; pancreatic lipase related protein 2; particle size

Indexed keywords

EXCIPIENT; GASTRIC LIPASE; LABRASOL; MACROGOL; MONOACYLGLYCEROL; PANCREATIC CARBOXYL ESTER HYDROLASE; PANCREATIC LIPASE RELATED PROTEIN 2; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; WATER;

ARTICLE; COLLOID; DRUG BIOAVAILABILITY; DRUG HYDROLYSIS; DRUG SOLUBILITY; ENZYME ACTIVITY; ENZYME SPECIFICITY; ENZYME STRUCTURE; ENZYME SUBSTRATE COMPLEX; IN VITRO STUDY; LIPID COMPOSITION; LIPOLYSIS; MICROEMULSION; PARTICLE SIZE; PRIORITY JOURNAL;

ANIMALS; CATTLE; COLLOIDS; DOGS; EMULSIONS; EXCIPIENTS; HUMANS; LIPASE; LIPIDS; LIPOLYSIS; PANCREAS; RECOMBINANT PROTEINS; SWINE;

EID: 84890546736     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-013-1053-0     Document Type: Article

References (62)

1. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004;58(3):173-82.
2. Charman SA, Charman WN, Rogge MC, Wilson TD, Dutko FJ, Pouton CW. Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound. Pharm Res. 1992;9(1):87-93.
3. Devani M, Ashford M, Craig DQ. The emulsification and solubilisation properties of polyglycolysed oils in self-emulsifying formulations. J Pharm Pharmacol. 2004;56(3):307-16.
4. Holm R, Porter CJ, Edwards GA, Mullertz A, Kristensen HG, Charman WN. Examination of oral absorption and lymphatic transport of halofantrine in a triple-cannulated canine model after administration in self-microemulsifying drug delivery systems (SMEDDS) containing structured triglycerides. Eur J Pharm Sci. 2003;20(1):91-7.
5. Khoo SM, Humberstone AJ, Porter CJH, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm. 1998;167(1-2):155-64.
6. Porter CJ, 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.
7. 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:S93-8.
8. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci. 2006;29:278-87.
9. Craig DQM, Lievens HSR, Pitt KG, Storey DE. An investigation into the physicochemical properties of self-emulsifying systems using low-frequency dielectric-spectroscopy, surface-tension measurements and particle size analysis. Int J Pharm. 1993;96(1-3):147-55.
10. Nazzal S, Smalyukh II, Lavrentovich OD, Khan MA. Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: mechanism and progress of emulsion formation. Int J Pharm. 2002;235(1-2):247-65.
11. Charman WN, Porter CJ, 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.
12. Fernandez S, Jannin V, Rodier JD, Ritter N, Mahler B, Carriere 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.
13. Fernandez S, Rodier JD, Ritter N, Mahler B, Demarne F, Carriere F, et al. Lipolysis of the semi-solid self-emulsifying excipient Gelucire 44/14 by digestive lipases. Biochim Biophys Acta. 2008;1781(8):367-75.
14. Bakala N'Goma JC, Amara S, Dridi K, Jannin V, Carriere F. Understanding the lipid-digestion processes in the GI tract before designing lipid-based drug-delivery systems. Ther Deliv. 2012;3(1):105-24.
15. 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.
16. Porter CJ, Kaukonen AM, Taillardat-Bertschinger A, Boyd BJ, O'Connor JM, Edwards GA, et al. Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: studies with halofantrine. J Pharm Sci. 2004;93:1110-21.
17. Williams HD, Sassene P, Kleberg K, Bakala-N'Goma JC, Calderone M, Jannin V, et al. 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. 2012;101(9):3360-80.
18. 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 I, II, IIIA, IIIB, and IV formulations during in vitro digestion. Mol Pharm. 2012;9(11):3286-300.
19. Ljusberg-Wahren H, Seier Nielsen F, Brogard M, Troedsson E, Mullertz A. Enzymatic characterization of lipid-based drug delivery systems. Int J Pharm. 2005;298(2):328-32.
20. Sek L, Boyd BJ, Charman WN, Porter CJ. Examination of the impact of a range of pluronic surfactants on the in-vitro solubilisation behaviour and oral bioavailability of lipidic formulations of atovaquone. J Pharm Pharmacol. 2006;58(6):809-20.
21. Sek L, Porter CJ, Charman WN. 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. 2001;25(3-4):651-61.
22. Sek L, Porter CJ, Kaukonen AM, Charman WN. Evaluation of the in-vitro digestion profiles of long and medium chain glycerides and the phase behaviour of their lipolytic products. J Pharm Pharmacol. 2002;54(1):29-41.
23. Cuine JF, Charman WN, Pouton CW, Edwards GA, Porter CJ. 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. 2007;24(4):748-57.
24. Cuine JF, McEvoy CL, Charman WN, Pouton CW, Edwards GA, Benameur H, et al. Evaluation of the impact of surfactant digestion on the bioavailability of danazol after oral administration of lipidic self-emulsifying formulations to dogs. J Pharm Sci. 2008;97(2):995-1012.
25. 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.
26. Gargouri Y, Pieroni G, Riviere C, Lowe PA, Sauniere 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.
27. Lengsfeld H, Beaumier-Gallon G, Chahinian H, De Caro A, Verger R, Laugier R, et al. Physiology of gastrointestinal lipolysis and therapeutical use of lipases and digestive lipase inhibitors. In: Müller G, Petry S, editors. Lipases and phospholipases in drug development. Weinheim: Wiley-VCH; 2004. p. 195-229.
28. 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.
29. 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.
30. Capolino P, Guérin C, Paume J, Giallo J, Ballester JM, Cavalier JF, et al. In vitro gastrointestinal lipolysis: replacement of human digestive lipases by a combination of rabbit gastric and porcine pancreatic extracts. Food Digestion. 2011;2:43-51.
31. Vors C, Capolino P, Guerin C, Meugnier E, Pesenti S, Chauvin MA, 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):537-46.
32. Eaimtrakarn S, Rama Prasad YV, Ohno T, Konishi T, Yoshikawa Y, Shibata N, et al. Absorption enhancing effect of Labrasol on the intestinal absorption of insulin in rats. J Drug Target. 2002;10(3):255-60.
33. Hu Z, Tawa R, Konishi T, Shibata N, Takada K. A novel emulsifier, Labrasol, enhances gastrointestinal absorption of gentamicin. Life Sci. 2001;69(24):2899-910.
34. Prasad YV, Puthli SP, Eaimtrakarn S, Ishida M, Yoshikawa Y, Shibata N, et al. Enhanced intestinal absorption of vancomycin with Labrasol and D-alpha-tocopheryl PEG 1000 succinate in rats. Int J Pharm. 2003;250(1):181-90.
35. Rama Prasad YV, Minamimoto T, Yoshikawa Y, Shibata N, Mori S, Matsuura A, et al. In situ intestinal absorption studies on low molecular weight heparin in rats using Labrasol as absorption enhancer. Int J Pharm. 2004;271(1-2):225-32.
36. Bandyopadhyay S, Katare OP, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B Biointerfaces. 2012;100:50-61.
37. Ragelle H, Crauste-Manciet S, Seguin J, Brossard D, Scherman D, Arnaud P, et al. Nanoemulsion formulation of fisetin improves bioavailability and antitumour activity in mice. Int J Pharm. 2012;427(2):452-9.
38. Kim DW, Kang JH, Oh DH, Yong CS, Choi HG. Development of novel flurbiprofen-loaded solid self-microemulsifying drug delivery system using gelatin as solid carrier. J Microencapsul. 2012;29(4):323-30.
39. Balakrishnan P, Lee BJ, Oh DH, Kim JO, Hong MJ, Jee JP, et al. Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm. 2009;72(3):539-45.
40. Kang MJ, Kim HS, Jeon HS, Park JH, Lee BS, Ahn BK, et al. In situ intestinal permeability and in vivo absorption characteristics of olmesartan medoxomil in self-microemulsifying drug delivery system. Drug Dev Ind Pharm. 2012;38(5):587-96.
41. Yan YD, Kim JA, Kwak MK, Yoo BK, Yong CS, Choi HG. Enhanced oral bioavailability of curcumin via a solid lipid-based self-emulsifying drug delivery system using a spray-drying technique. Biol Pharm Bull. 2011;34(8):1179-86.
42. Shen Y, Lu Y, Jv M, Hu J, Li Q, Tu J. Enhancing effect of Labrasol on the intestinal absorption of ganciclovir in rats. Drug Dev Ind Pharm. 2011;37(12):1415-21.
43. Green CE, Swezey R, Bakke J, Shinn W, Furimsky A, Bejugam N, et al. Improved oral bioavailability in rats of SR13668, a novel anti-cancer agent. Cancer Chemother Pharmacol. 2011;67(5):995-1006.
44. Barakat NS. Enhanced oral bioavailability of etodolac by self-emulsifying systems: in-vitro and in-vivo evaluation. J Pharm Pharmacol. 2010;62(2):173-80.
45. Venkatesh G, Majid MI, Mansor SM, Nair NK, Croft SL, Navaratnam V. In vitro and in vivo evaluation of self-microemulsifying drug delivery system of buparvaquone. Drug Dev Ind Pharm. 2010;36(6):735-45.
46. Balakrishnan P, Lee BJ, Oh DH, Kim JO, Lee YI, Kim DD, et al. Enhanced oral bioavailability of coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm. 2009;374(1-2):66-72.
47. Yi T, Wan J, Xu H, Yang X. A new solid self-microemulsifying formulation prepared by spray-drying to improve the oral bioavailability of poorly water soluble drugs. Eur J Pharm Biopharm. 2008;70(2):439-44.
48. Eydoux C, De Caro J, Ferrato F, Boullanger P, Lafont D, Laugier R, et al. Further biochemical characterization of human pancreatic lipase-related protein 2 expressed in yeast cells. J Lipid Res. 2007;48(7):1539-49.
49. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
50. Tuvignon N, Abousalham A, Tocques F, De Caro J, De Caro A, Laugier R, et al. Development of an indirect method for measuring porcine pancreatic lipase in human duodenal fluid. Anal Biochem. 2008;383(2):289-95.
51. Mitchell DA, Rodriguez JA, Carriere F, Baratti J, Krieger N. An analytical method for determining relative specificities for sequential reactions catalyzed by the same enzyme: application to the hydrolysis of triacylglycerols by lipases. J Biotechnol. 2008;133(3):343-50.
52. Carrière F, Moreau H, Raphel V, Laugier R, Bénicourt C, Junien J-L, et al. Purification and biochemical characterization of dog gastric lipase. Eur J Biochem. 1991;202(1):75-83.
53. Carrière F, Raphel V, Moreau H, Bernadac A, Devaux M-A, Grimaud R, et al. Dog gastric lipase: stimulation of its secretion in vivo and cytolocalization in mucous pit cells. Gastroenterology. 1992;102(5):1535-45.
54. Carrière F, Laugier R, Barrowman JA, Douchet I, Priymenko N, Verger R. Gastric and pancreatic lipase levels during a test meal in dogs. Scand J Gastroenterol. 1993;28(5):443-54.
55. Roussel A, Miled N, Berti-Dupuis L, Riviere 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.
56. De Caro J, Eydoux C, Cherif S, Lebrun R, Gargouri Y, Carriere F, et al. Occurrence of pancreatic lipase-related protein-2 in various species and its relationship with herbivore diet. Comp Biochem Physiol B Biochem Mol Biol. 2008;150(1):1-9.
57. Fatouros DG, Bergenstahl B, Mullertz A. Morphological observations on a lipid-based drug delivery system during in vitro digestion. Eur J Pharm Sci. 2007;31(2):85-94.
58. Fatouros DG, Deen GR, Arleth L, Bergenstahl B, Nielsen FS, Pedersen JS, et al. Structural development of self nano emulsifying drug delivery systems (SNEDDS) during in vitro lipid digestion monitored by small-angle X-ray scattering. Pharm Res. 2007;24(10):1844-53.
59. Amara S, Lafont D, Fiorentino B, Boullanger P, Carriere F, De Caro A. Continuous measurement of galactolipid hydrolysis by pancreatic lipolytic enzymes using the pH-stat technique and a medium chain monogalactosyl diglyceride as substrate. Biochim Biophys Acta. 2009;1791(10):983-90.
60. Fernandez S, Najjar A, Robert S, Rodier JD, Mahler B, Demarne F, et al. Specific assay of carboxyl ester hydrolase using PEG esters as substrate. Analytical Methods. 2010;2(8):1013-9.
61. 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.
62. Benzonana G, Desnuelle P. Kinetic study of the action of pancreatic lipase on emulsified triglycerides. Enzymology assay in heterogeneous medium. Biochim Biophys Acta. 1965;105(1):121-36.