The role of citric acid in oral peptide and protein formulations: Relationship between calcium chelation and proteolysis inhibition

European Journal of Pharmaceutics and Biopharmaceutics

Volumn 86, Issue 3, 2014, Pages 544-551

  Welling, Søren H ^a,b   Hubálek, František ^a   Jacobsen, Jette ^b   Brayden, David J ^c   Rahbek, Ulrik L ^a   Buckley, Stephen T ^a  

^a NOVO NORDISK A S   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c UNIVERSITY COLLEGE DUBLIN   (Ireland)

Author keywords

Chelation; Citric acid; Insulin; Intestinal drug permeability; Oral peptide delivery; Proteolysis inhibition

Indexed keywords

CALCIUM; CARNITINE; CITRIC ACID; INSULIN; PENETRATION ENHANCING AGENT; PEPTIDE; BOVINE SERUM ALBUMIN; CALCIUM CHELATING AGENT;

ARTICLE; CALCIUM ELECTRODE; COMPUTER MODEL; CONTROLLED STUDY; DEPLETION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG FORMULATION; DRUG PENETRATION; ELECTRIC RESISTANCE; HUMAN; HUMAN CELL; IN VITRO STUDY; INSULIN DEGRADATION; ION SELECTIVE ELECTRODE; PH; PROTEIN DEGRADATION; ANIMAL; CACO 2 CELL LINE; DRUG EFFECTS; INTESTINE MUCOSA; MALE; MEDICINAL CHEMISTRY; METABOLISM; ORAL DRUG ADMINISTRATION; RAT; WISTAR RAT;

ADMINISTRATION, ORAL; ANIMALS; CACO-2 CELLS; CALCIUM; CALCIUM CHELATING AGENTS; CHEMISTRY, PHARMACEUTICAL; CITRIC ACID; HUMANS; INSULIN; INTESTINAL MUCOSA; MALE; PEPTIDES; PROTEOLYSIS; RATS; RATS, WISTAR; SERUM ALBUMIN, BOVINE;

EID: 84898424706     PISSN: 09396411     EISSN: 18733441     Source Type: Journal    
DOI: 10.1016/j.ejpb.2013.12.017     Document Type: Article

References (34)

1. A.D. McLaren, and E.F. Estermann Influence of pH on the activity of chymotrypsin at a solid-liquid interface Arch. Biochem. Biophys. 68 1957 157 160
2. R. Schilling, and A. Mitra Degradation of insulin by trypsin and alpha-chymotrypsin Pharm. Res. 8 1991 721 727
3. N. Binkley, M. Bolognese, A. Sidorowicz-Bialynicka, T. Vally, R. Trout, C. Miller, C.E. Buben, J.P. Gilligan, and D.S. Krause A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the oral calcitonin in postmenopausal osteoporosis (ORACAL) trial J. Bone Miner. Res. 27 2012 1821 1829
4. J.P.F. Bai, L.L. Chang, and J.H. Guo Effects of polyacrylic polymers on the lumenal proteolysis of peptide drugs in the colon J. Pharm. Sci. 84 1995 1291 1294
5. Y.H. Lee, and P.J. Sinko Oral delivery of salmon calcitonin Adv. Drug Deliv. Rev. 42 2000 225 238
6. P. Sinko, Y.H. Lee, V. Makhey, G. Leesman, J. Sutyak, H. Yu, B. Perry, C. Smith, P. Hu, E. Wagner, L. Falzone, L. McWhorter, J. Gilligan, and W. Stern Biopharmaceutical approaches for developing and assessing oral peptide delivery strategies and systems: in vitro permeability and in vivo oral absorption of salmon calcitonin Pharm. Res. 16 1999 527 533
7. N.M. Mehta Oral Delivery and recombinant production of peptide hormones Part I: making oral delivery possible BioPharm Int. 17 2004
8. M.J. Cho, J.F. Scieszka, and P.S. Burton Citric acid as an adjuvant for transepithelial transport Int. J. Pharm. 52 1989 79 81
9. M. Grant, and M.A. Leone-Bay Peptide therapeutics: it's all in the delivery Ther. Deliv. 3 2012 981 996
10. D.P. Froment, B.A. Molitoris, B. Buddington, N. Miller, and A.C. Alfrey Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate Kidney Int. 36 1989 978 984
11. C.R. Nolan, J.R. Califano, and C.A. Butzin Influence of calcium acetate or calcium citrate on intestinal aluminum absorption Kidney Int. 38 1990 937 941
12. R.P. Singh, Y.D. Yeboah, E.R. Pambid, and P. Debayle Stability constant of the calcium-citrate(3-) ion pair complex J. Chem. Eng. Data 36 1991 52 54
13. A.J. Meyer, and M. Popp Free Ca2+ in tissue 22+ -selective electrodes J. Exp. Bot. 48 1997 337 344
14. J.L. Meyer Formation constants for interaction of citrate with calcium and magnesium ions Anal. Biochem. 62 1974 295 300
15. A.W. Cuthbert, and H.S. Margolius Kinins stimulate net chloride secretion by the rat colon Br. J. Pharmacol. 75 1982 587 598
16. G. Borchard, H.L. Lueβen, A.G. de Boer, J.C. Verhoef, C.M. Lehr, and H.E. Junginger The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro J. Control. Release. 39 1996 131 138
17. Y.H. Lee, B. Perry, S. Labruno, H. Lee, W. Stern, L. Falzone, and P. Sinko Impact of regional intestinal pH modulation on absorption of peptide drugs: oral absorption studies of salmon calcitonin in beagle dogs Pharm. Res. 16 1999 1233 1239
18. M. Tomita, M. Hayashi, and S. Awazu Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarnitine in Caco-2 cells J. Pharm. Sci. 85 1996 608 611
19. A.B.J. Noach, Y. Kurosaki, M.C.M. Blom-Roosemalen, A.G. de Boer, and D.D. Breimer Cell-polarity dependent effect of chelation on the paracellular permeability of confluent caco-2 cell monolayers Int. J. Pharm. 90 1993 229 237
20. T. Sasaki, and H. Kise Increase of catalytic activity of α-chymotrypsin by metal salts for transesterification of an amino acid ester in ethanol Biosci. Biotechnol. Biochem. 61 1997 1196 1197
21. J.P. Bai, and L.L. Chang Transepithelial transport of insulin: I. Insulin degradation by insulin-degrading enzyme in small intestinal epithelium Pharm. Res. 12 1995 1171 1175
22. G.P. Carino, and E. Mathiowitz Oral insulin delivery Adv. Drug Deliv. Rev. 35 1999 249 257
23. A.C. Chao, M.T. Taylor, P.E. Daddona, M. Broughall, and J.A. Fix Molecular weight-dependent paracellular transport of fluorescent model compounds induced by palmitoylcarnitine chloride across the human intestinal epithelial cell line Caco-2 J. Drug Target. 6 1998 37 43
24. J.A. Fix, K. Engle, P.A. Porter, P.S. Leppert, S.J. Selk, C.R. Gardner, and J. Alexander Acylcarnitines: drug absorption-enhancing agents in the gastrointestinal tract Am. J. Physiol. 251 1986 G332-40
25. E.L. LeCluyse, S.C. Sutton, and J.A. Fix In vitro effects of long-chain acylcarnitines on the permeability, transepithelial electrical resistance and morphology of rat colonic mucosa J. Pharmacol. Exp. Ther. 265 1993 955 962
26. H. Okada, I. Yamazaki, Y. Ogawa, S. Hirai, T. Yashiki, and H. Mima Vaginal absorption of a potent luteinizing hormone-releasing hormone analog (leuprolide) in rats I: Absorption by various routes and absorption enhancement J. Pharm. Sci. 71 1982 1367 1371
27. H. Ichikawa, and N.A. Peppas Novel complexation hydrogels for oral peptide delivery: in vitro evaluation of their cytocompatibility and insulin-transport enhancing effects using Caco-2 cell monolayers J. Biomed. Mater. Res. 67A 2003 609 617
28. A.C. Foss, and N.A. Peppas Investigation of the cytotoxicity and insulin transport of acrylic-based copolymer protein delivery systems in contact with caco-2 cultures Eur. J. Pharm. Biopharm. 57 2004 447 455
29. K.H. Song, S.J. Chung, and C.K. Shim Preparation and evaluation of proliposomes containing salmon calcitonin J. Control. Release. 84 2002 27 37
30. P.S. Hiremath, K.S. Soppimath, and G.V. Betageri Proliposomes of exemestane for improved oral delivery: formulation and in vitro evaluation using PAMPA, Caco-2 and rat intestine Int. J. Pharm. 380 2009 96 104
31. R. Shah, and M. Khan Regional permeability of salmon calcitonin in isolated rat gastrointestinal tracts: transport mechanism using Caco-2 cell monolayer AAPS J. 6 2004 36 40
32. M. Kidron, H. Bar-On, E.M. Berry, and E. Ziv The absorption of insulin from various regions of the rat intestine Life Sci. 31 1982 2837 2841
33. E. Karasulu, A. Yavasglu, Z. Evrensanal, Y. Uyanikgil, and H.Y. Karasulu Permeation studies and histological examination of sheep nasal mucosa following administration of different nasal formulations with or without absorption enhancers Drug. Deliv. 15 2008 219 225
34. A. Allen, and G. Flemstrom Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin Am. J. Physiol. Cell Physiol. 288 2005