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Self-Nanoemulsifying Drug Delivery System of Lutein: Physicochemical Properties and Effect on Bioavailability of Warfarin

  • Received : 2013.01.25
  • Accepted : 2013.02.27
  • Published : 2013.03.31

Abstract

Objective of present study was to prepare and characterize self-nanoemulsifying drug delivery system (SNEDDS) of lutein and to evaluate its effect on bioavailability of warfarin. The SNEDDS was prepared using an oil, a surfactant, and co-surfactants with optimal composition based on pseudo-ternary phase diagram. Effect of the SNEDDS on the bioavailability of warfarin was performed using Sprague Dawley rats. Lutein was successfully formulated as SNEDDS for immediate self-emulsification and dissolution by using combination of Peceol as oil, Labrasol as surfactant, and Transcutol-HP or Lutrol-E400 as co-surfactant. Almost complete dissolution was achieved after 15 min while lutein was not detectable from the lutein powder or intra-capsule content of a commercial formulation. SNEDDS formulation of lutein affected bioavailability of warfarin, showing about 10% increase in $C_{max}$ and AUC of the drug in rats while lutein as non-SNEDDS did not alter these parameters. Although exact mechanism is not yet elucidated, it appears that surfactant and co-surfactant used for SNEDDS formulation caused disturbance in the anatomy of small intestinal microvilli, leading to permeability change of the mucosal membrane. Based on this finding, it is suggested that drugs with narrow therapeutic range such as warfarin be administered with caution to avoid undesirable drug interaction due to large amount of surfactants contained in SNEDDS.

Keywords

References

  1. Aman, R., Biehl, J., Carle, R., Conrad, J., Beifuss, U. and Schieber, A. (2005) Application of HPLC coupled with DAD, APcI-MS and NMR to the analysis of lutein and zeaxanthin stereoisomers in thermally processed vegetables. Food Chem. 92, 753-763. https://doi.org/10.1016/j.foodchem.2004.10.031
  2. Baskaran, V., Sugawara, T. and Nagao, A. (2003) Phospholipids affect the intestinal absorption of carotenoids in mice. Lipids 38, 705-711. https://doi.org/10.1007/s11745-003-1118-5
  3. Brown, L., Rimm, E., Seddon, J., Giovannucci, E., Chasan-Taber, L., Spiegelman, D., Willett, W. and Hankinson, S. (1999) A prospective study of carotenoid intake and risk of cataract extraction in US men. Am. J. Clin. Nutr. 70, 517-524. https://doi.org/10.1093/ajcn/70.4.517
  4. Cha, K. H., Lee, J. Y., Song, D. G., Kim, S. M., Lee, D. U., Jeon, J. Y. and Pan, C. H. (2011) Effect of microfluidization on in vitro micellization and intestinal cell uptake of lutein from Chlorella vulgaris. J. Agric. Food Chem. 59, 8670-8674. https://doi.org/10.1021/jf2019243
  5. Chakraborty, S., Shukla, D., Mishra, B. and Singh, S. (2009) Lipid: an emerging platform for oral delivery of drugs with poor bioavailability. Eur. J. Pharm. Biopharm. 73, 1-15. https://doi.org/10.1016/j.ejpb.2009.06.001
  6. Chasan-Taber, L., Willett, W., Seddon, J., Stampfer, M., Rosner, B., Colditz, G., Speizer, F. and Hankinson, S. (1999) A prospective study of carotenoid and Vitamin A intakes and risk of cataract extraction in US women. Am. J. Clin. Nutr. 70, 509-516. https://doi.org/10.1093/ajcn/70.4.509
  7. Chung, H. Y., Rasmussen, H. M. and Johnson, E. J. (2004) Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men. J. Nutr. 134, 1887-1893. https://doi.org/10.1093/jn/134.8.1887
  8. Gale, C., Hall, N., Phillips, D. and Martyn, C. (2001) Plasma antioxidant vitamins and carotenoids and age-related cataract. Ophthalmology 108, 1992-1998. https://doi.org/10.1016/S0161-6420(01)00833-8
  9. Ghate, S. R., Biskupiak, J. E., Ye, X., Hagan, M., Kwong, W. J., Fox, E. S. and Brixner, D. I. (2011) Hemorrhagic and thrombotic events associated with generic substitution of warfarin in patients with atrial fibrillation: a retrospective analysis. Ann. Pharmacother. 45, 701-712. https://doi.org/10.1345/aph.1P593
  10. Goltz, S. R., Campbell, W. W., Chitchumroonchokchai, C., Failla, M. L. and Ferruzzi, M. G. (2012) Meal triacylglycerol profile modulates postprandial absorption of carotenoids in humans. Mol. Nutr. Food Res. 56, 866-877. https://doi.org/10.1002/mnfr.201100687
  11. Graefe-Mody, E. U., Brand, T., Ring, A., Withopf, B., Stangier, J., Iovino, M. and Woerle, H. J. (2011) Effect of linagliptin on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. Int. J. Clin. Pharmacol. Ther. 49, 300-310. https://doi.org/10.5414/CP201507
  12. Granado, F., Olmedilla, B., Blanco, I. and Rojas-Hidalgo, E. (1996) Major fruit and vegetable contributors to the main serum carotenoids in the Spanish diet. Eur. J. Clin. Nutr. 50, 246-250.
  13. Granado-Lorencio, F., Herrero-Barbudo, C., Olmedilla-Alonso, B., Blanco-Navarro, I. and Perez-Sacristan, B. (2010) Lutein bioavailability from lutein ester-fortified fermented milk: in vivo and in vitro study. J. Nutr. Biochem. 21, 133-139. https://doi.org/10.1016/j.jnutbio.2008.12.002
  14. Haines, S. T. (2011) Substituting warfarin products: what's the source of the problem? Ann. Pharmacother. 45, 807-809. https://doi.org/10.1345/aph.1Q063
  15. Hankinson, S., Stampfer, M., Seddon, J., Colditz, G., Rosner, B., Speizer, F. and Willett, W. (1992) Nutrient intake and cataract extraction in women: a prospective study. BMJ 305, 335-339. https://doi.org/10.1136/bmj.305.6849.335
  16. Johnson, E. (2004) A biological role of lutein. Food Rev. Int. 20, 1-16. https://doi.org/10.1081/FRI-120028826
  17. Khachik, F. (1995) Process for isolation, purification, and recrystallization of lutein from saponified marigolds oleoresin and uses thereof. U.S. Patent 5382714.
  18. Kommuru, T., Gurley, B., Khan, M. and Reddy, I. (2001) Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int. J. Pharm. 212, 233-246. https://doi.org/10.1016/S0378-5173(00)00614-1
  19. Lakshminarayana, R., Raju, M., Krishnakantha, T. and Baskaran, V. (2006) Enhanced lutein bioavailability by lyso-phosphatidylcholine in rats. Mol. Cell. Biochem. 281, 103-110. https://doi.org/10.1007/s11010-006-1337-3
  20. Landrum, J. and Bone, R. (2001) Lutein, zeaxanthin, and the macular pigment. Arch. Biochem. Biophys. 385, 28-40. https://doi.org/10.1006/abbi.2000.2171
  21. Lyle, B., Mares-Perlman, J., Klein, B., Klein, R. and Greger, J. (1999) Antioxidant intake and risk of incident age-related nuclear cataracts in the Beaver Dam Eye Study. Am. J. Epidemiol. 149, 801-809. https://doi.org/10.1093/oxfordjournals.aje.a009895
  22. Ma, H., Zhao, Q., Wang, Y., Guo, T., An, Y. and Shi, G. (2012) Design and evaluation of self-emulsifying drug delivery systems of Rhizoma corydalis decumbentis extracts. Drug Dev. Ind. Pharm. 38, 1200-1206. https://doi.org/10.3109/03639045.2011.643897
  23. Malhotra, B., Alvey, C., Gong, J., Li, X., Duczynski, G. and Gandelman, K. (2011) Effects of fesoterodine on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. Br. J. Clin. Pharmacol. 72, 257-262. https://doi.org/10.1111/j.1365-2125.2011.03989.x
  24. Mamatha, B. S. and Baskaran, V. (2011) Effect of micellar lipids, dietary fiber and ${\beta}$-carotene on lutein bioavailability in aged rats with lutein deficiency. Nutrition 27, 960-966. https://doi.org/10.1016/j.nut.2010.10.011
  25. Mares-Perlman, J., Fisher, A., Palta, M., Block, G., Millen, A. and Wright, J. (2001) Lutein and zeaxanthin in the diet and serum and their relation to age-related maculopathy in the third national health and nutrition examination survey. Am. J. Epidemiol. 153, 424-432. https://doi.org/10.1093/aje/153.5.424
  26. Marisiddaiah, R. and Baskaran, V. (2009) Bioefficacy of beta-carotene is improved in rats after solubilized as equimolar dose of beta-carotene and lutein in phospholipid-mixed micelles. Nutr. Res. 29, 588-595. https://doi.org/10.1016/j.nutres.2009.07.005
  27. Mitri, K., Shegokar, R., Gohla, S., Anselmi, C. and Muller, R. H. (2011) Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int. J. Pharm. 420, 141-146. https://doi.org/10.1016/j.ijpharm.2011.08.026
  28. O'Neill, M., Carroll, Y., Corridan, B., Olmedilla, B., Granado, F., Blanco, I., Van den Berg, H., Hininger, I., Rousell, A., Chopra, M., Southon, S. and Thurnham, D. (2001) A European carotenoid database to assess carotenoid intakes and its use in a five-country comparative study. Br. J. Nutr. 85, 499-507. https://doi.org/10.1079/BJN2000284
  29. Pouton, C. W. (2006) Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm. Sci. 29, 278-287.
  30. Seddon, J., Ajani, U., Sperduto, R., Hiller, R., Blair, N., Burton, T., Farber, M., Gragoudas, E., Haller, J., Miller, D., Yannuzzi, L. and Willett, W. (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 272, 1413-1420. https://doi.org/10.1001/jama.1994.03520180037032
  31. Shanmugam, S., Baskaran, R., Balakrishnan, P., Thapa, P., Yong, C. S. and Yoo, B. K. (2011) Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein. Eur. J. Pharm. Biopharm. 79, 250-257. https://doi.org/10.1016/j.ejpb.2011.04.012
  32. Shao, B., Tang, J., Ji, H., Liu, H., Liu, Y., Zhu, D. and Wu, L. (2010) Enhanced oral bioavailability of Wurenchun (Fructus Schisandrae Chinensis extracts) by self-emulsifying drug delivery systems. Drug Dev. Ind. Pharm. 36, 1356-1363. https://doi.org/10.3109/03639045.2010.480975
  33. Singh, A. K., Chaurasiya, A., Singh, M., Upadhyay, S. C., Mukherjee, R. and Khar, R. K. (2008) Exemestane loaded self-microemulsifying drug delivery system (SMEDDS): development and optimization. AAPS PharmSciTech. 9, 628-634. https://doi.org/10.1208/s12249-008-9080-6
  34. Thi, T. D., Van Speybroeck, M., Barillaro, V., Martens, J., Annaert, P., Augustijns, P., Van Humbeeck, J., Vermant, J. and Van den Mooter, G. (2009) Formulate-ability of ten compounds with different physicochemical profiles in SMEDDS. Eur. J. Pharm. Sci. 38, 479-488. https://doi.org/10.1016/j.ejps.2009.09.012
  35. Vithlani, S., Sarraf, S. and Chaw, C. S. (2012) Formulation and in vitro evaluation of self-emulsifying formulations of Cinnarizine. Drug Dev. Ind. Pharm. 38, 1188-1194. https://doi.org/10.3109/03639045.2011.643895
  36. Wei, Y., Zhang, T., Xu, G. and Ito, Y. (2003) Application of CCC for the separation of lutein from a crude extract of marigold flower petals. J. Liq. Chromatogr. Relat. Technol. 26, 1659-1669. https://doi.org/10.1081/JLC-120021274
  37. Wu, Z., Guo, D., Deng, L., Zhang, Y., Yang, Q. and Chen, J. (2011) Preparation and evaluation of a self-emulsifying drug delivery system of etoposide-phospholipid complex. Drug Dev. Ind. Pharm. 37, 103-112. https://doi.org/10.3109/03639045.2010.495752
  38. Yan, Y., Kim, J., Kwak, M., Yoo, B., Yong, C. and Choi, H. (2011) Enhanced oral bioavailability of curcumin via a solid lipid-based self-emulsifying drug delivery system using a spray-drying technique. Biol. Pharm. Bull. 34, 1179-1186. https://doi.org/10.1248/bpb.34.1179
  39. Yonekura, L. and Nagao, A. (2007) Intestinal absorption of dietary carotenoids. Mol. Nutr. Food Res. 51, 107-115. https://doi.org/10.1002/mnfr.200600145
  40. Yoo, J. H., Shanmugam, S., Thapa, P., Lee, E. S., Balakrishnan, P., Baskaran, R., Yoon, S. K., Choi, H. G., Yong, C. S., Yoo, B. K. and Han, K. (2010) Novel self-nanoemulsifying drug delivery system for enhanced solubility and dissolution of lutein. Arch. Pharm. Res. 33, 417-426. https://doi.org/10.1007/s12272-010-0311-5
  41. Zhou, L., Wang, S., Zhang, Z., Lau, B. S., Fung, K. P., Leung, P. C. and Zuo, Z. (2012) Pharmacokinetic and pharmacodynamic interaction of Danshen-Gegen extract with warfarin and aspirin. J. Ethnopharmacol. 143, 648-655. https://doi.org/10.1016/j.jep.2012.07.029

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