Developing the drugs as amphiphilic lipid complexes is a potential approach for improving therapeutic efficacy of the drugs by increasing solubility, reducing drug crystallinity, modifying dissolution behavior (sustained or controlled release), and improving bioavailability. Emodin (1,3,8-trihydroxy-6-methylanthraquinone), an anthranoid derivative, shows several biological effects like antimicrobial, antidiuretic, anti-cancerous, and potent antioxidant but due to poor solubility, the dissolution restrains its valuable importance. To overcome this limitation, the emodin–phospholipid complex was developed and investigated by thermal analysis (differential scanning calorimetry), crystallographic (X-ray diffractography), surface morphology (scanning electron microscopy), spectroscopic methods (FT-IR, 1H-NMR), solubility, and the dissolution (in vitro drug release) study. The phospholipid complex of emodin was found, fluffy and porous with rough surface morphology in the SEM. FT-IR, 1H-NMR, DSC, and X-RPD data confirmed the formation of the complex. The water and n-octanol solubility of emodin was improved from 2.25 to 9.97 and 53.45 to 77.62 μg/ml, respectively, in the prepared complex. The improved dissolution was shown by the phospholipid complex. Based on the results of the study, it can be concluded that the phospholipid complex may be considered as promising drug delivery system for improving the overall absorption and bioavailability of the emodin molecule.
1. Mueller, SO, Schmitt, M, Dekant, W, Stopper, H, Schlatter, J, Schreier, P, Lutz, WK. Occurrence of emodin, crysophanol and physcion in vegetables, herbs and liquors, genotoxicity and anti-genotoxicity of the anthraquinones and of the whole plant. Food Chem Toxicol. 1999;37:481–491. .
2. Fratta, D, Simi, S, Rainaldi, G, Gervasi, PG. Role of cytochrome p-450 isoenzymes in the bioactivation of hydroxy anthraquinones. Anticancer Res. 1994;14:2597–2603.
3. Gu, J, Zhang, X, Fei, Z, Wen, A, Qin, S, Yi, S, Chen, Y, Li, X. Rhubarb extracts in treating complication of severe cerebral injury. Chin Med J. 2000;113:529–531.
4. Huang, LY, Hu, JD, Chen, XJ, Zhu, LF, Hu, HL. Effect of emodin on the proliferation inhibition and apoptosis inactivation in HL-60 cells and the involvement of c-myc gene. Zhonghua Xue Ye Xue Za Zhi. 2005;26:348–351.
5. Liu, R, Zhang, J, Liang, M, Zhang, W, Yan, S, Lin, M. Simultaneous analysis of eight bioactive compounds in danning tablet by HPLC-ESI-MS and HPLC-UV. J Pharm Biomed Anal. 2007;43:1007–1012. .
6. Yim, H, Lee, YH, Lee, CH, Lee, SK. Emodin an anthraquinone derivative isolated from the rhizomes of Rheum palmatum, selectively inhibits the activity of casein kinase II as a competitive inhibitor. Planta Med. 1999;65: 1 9–13. .
7. Lin, CC, Chang, CH, Yang, JJ, Namba, T, Hattory, M. Hepatoprotective effect of emodin from Ventilago leiocarpa. J Ethnopharmacol. 1996;52: 2 107–111. .
8. Wang, XM, Ren, Y. Rheum tanguticum, an endangered medicinal plant endemic to China. J Med Plants Res. 2009;3: 13 1195–1203.
9. Koyama, M, Kelly, TR, Watanabe, KA. Novel type of potential anticancer agents derived from crysophanol and emodin. J Med Chem. 1988;31:283–284. .
10. Zhang, L, Hung, MC. Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Oncogene. 1996;12:571–576.
11. Zhang, L, Chang, CJ, Bacus, SS, Hung, MC. Suppressed transformation and induced differentiation of HER-2/neu-overexpressing breast cancer cells by emodin. Cancer Res. 1995;55:3890–3896.
12. Zhang, L, Lau, YK, Xi, L, Hong, RL, Kim, DS, Chen, CF, Hortobagyi, GN, Chang, CJ, Hung, MC. Tyrosine kinase inhibitor, emodin and its derivative repress HER-2/neu-induced cellular transformation and metastasis-associated properties. Oncogene. 1998;16:2855–2863. .
13. Sydiskis, RJ, Owen, DG, Lohr, JL, Rosler, KH, Blomster, RN. Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother. 1991;35:2463–2466.
14. Zhou, XM, Chen, QH. Biochemical study of Chinese rhubarb XXII. Inhibitory effect of anthraquinone derivatives on sodium-potassium-ATPase of a rabbit renal medulla and their diuretic action. Acta Pharm Sin. 1988;23:17–20.
15. Huang, HC, Chu, SH, Chao-Lee, PD. Vasorelaxants from Chinese herbs, emodin and scoparone, possess immuno-suppressive properties. Eur J Pharmacol. 1991;198:211–213. .
16. Fujimoto, H, Satoh, Y, Yamaguchi, K, Yamazaki, M. Manoamine oxidase inhibitory constituents from Anixiella micropertusa. Chem Pharm Bull. 1998;46:1506–1510. .
17. Kong, LD, Christopher, HKC, Tan, RX. Inhibition of MAO A and B by some plant derived alkaloids, phenols and anthraquinones. J Ethnopharmacol. 2004;91: 2–3 351–355. .
18. Jayasuriya, H, Koonchanok, NM, Geahlen, RL, McLaughlin, JL, Chang, CJ. Emodin a Protein tyrosin kinase inhibitor from Polygonum cuspidatum. J Nat Prod. 1992;55:696–698. .
19. Kumar, A, Dhawan, S, Aggarwal, BB. Emodin (3-methyl-1,6,8-trihydroxy-anthraquinone) inhibits TNF-induced NF-kB activation, IkB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells. Oncogene. 1998;17:913–918. .
20. Ma, T, Qi, QH, Xu, J, Dong, ZL, Yang, WX. Signal pathways involved in emodin-induced contraction of smooth muscle cells from rat colon. World J Gastroenterol. 2004;10:1476–1479.
21. Ali, S, Watson, MS, Osborne, RH. The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine. Auton Autacoid Pharmacol. 2004;24:103–105. .
22. Huang, HC, Lee, CR, Chao, PD, Chen, CC, Chu, SH. Vasorelaxant effect of emodin, an anthraquinone from a Chinese herb. Eur J Pharmacol. 1991;205:289–294. .
23. Li, Y, Duan, J, Guo, T, Xie, W, Yan, S, Li, B, Zhou, Y, Chen, Y. In vivo pharmacokinetics comparisons of icariin, emodin and psoralen from Gan-kang granules and extracts of Herba Epimedii, Nepal dock root, Ficus hirta yahl. J Ethnopharmacol. 2009;124: 3 522–529. .
24. Teng, ZH, Zhou, SY, Yang, RT, Liu, XY, Liu, RW, Yang, X, Zhang, HBL, Yang, JY, Cao, DY, Mei, QB. Quantitation assay for absorption and first-pass metabolism of emodin in isolated rat small intestine using liquid chromatography-tandem mass spectrometry. Biol Pharm Bull. 2007;30: 9 1628–1633. .
25. Liu, W, Tang, L, Ye, L, Cai, Z, Xia, B, Zhang, J, Hu, M, Liu, Z. Species and gender differences affect the metabolism of emodin via glucuronidation. AAPS J. 2010;12: 3 424–436. .
26. Wang, GH, Nie, QX, Li, H, Zang, C, Zhang, BX, Zhao, XM. Comparative study on in vitro drug-release between Tuizhang ophthalmic gel and Tuizhang oculentum. Zhongguo Zhong Yao Za Zhi. 2007;32:683–687.
27. Leuner, C, Dressmann, J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2002;54:107–112. .
28. Rabinow, BE. Nanosuspension in drug delivery. Nat Rev Drug Discov. 2004;3:785–796. .
29. Nijlen, TV, Brennan, K, Mooter, VG, Blaton, N, Kinget, R, Augustijns, P. Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions. Int J Pharm. 2003;254:173–181. .
30. Nokhodchi, A. The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts. J Pharm Pharm Sci. 2005;8:18–25.
31. Murdande, SB, Pikal, MJ, Shankar, RM, Bogner, RH. Aqueous solubility of crystalline and amorphous drugs: challenges in measurement. Pharm Dev Technol. 2011;16: 3 187–200. .
32. Duan, HG, Wei, YH, Li, BX, Qin, HY, Wu, XA. Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000. Drug Develop Res. 2009;70: 5 363–369. .
33. Aigner Z , Heinrich R, Sipos E, Farkas G, Ciurba A, Berkesi O, Szabo-Revesz P. Compatibility studies of aceclofenac with retard tablet excipients by means of thermal and FT-IR spectroscopic methods. J Therm Ana Calorim. 2010; .
34. Yu PF , zheng Q, Wu B, Yang M, Wang MS, Zhang HY, Hu PY, Wu ZF. Process optimization by response surface design and characterization study on geniposide pharmacosomes. Pharm dev Technol. 2010; .
35. Venema, FR, Weringa, WD. The interactions of phospholipid vesicles with some anti-inflammatory agents. J Colloid Interf Sci. 1988;125: 2 484–492. .
36. Semalty, A, Semalty, M, Rawat, MSM, Federico, F. Supramolecular phospholipids-polyphenolic interactions: The PHYTOSOME® strategy to improve the bioavailability of phytochemicals. Fitoterapia. 2010;81:306–314. .
37. Semalty, A, Semalty, M, Rawat, BS, Singh, D, Rawat, MSM. Pharmacosomes: the lipid based novel drug delivery system. Expert Opin Drug Deliv. 2009;6: 6 599–612. .
38. PM Kidd Ph D . Phosphatidylcholine: a superior protectant against liver damage. Altern Med Rev. 1996;1: 4 258–274.
39. Yue, PF, Yuan, HL, Xie, H, Xiao, XH, Yang, M, Liao, MX, Zhu, WF, Cai, PL. Preparation, characterization, and bioavailability of ursodeoxycholic acid-phospholipid complex in vivo. Drug Dev Ind Pharm. 2008;34: 7 708–718. .
40. Yanyu, X, Yunmei, S, Zhipeng, C, Qineng, P. 2006 The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm. 307:77–82. .
41. Maiti, K, Mukherjee, K, Gantait, A, Saha, BP, Mukherjee, PK. Curcumin-phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm. 2007;330: 1–2 155–163. .
42. Semalty, A, Semalty, M, Singh, D, Rawat, MSM. Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery. J Incl Phenom Mac Chem. 2010;67: 3 253–260. .
43. Li, Y, Yang, DJ, Chen, SL, Chen, SB, Chan, ASC. Comparative physicochemical characterization of phospholipids complex of puerarin formulated by conventional and supercritical methods. Pharm Res. 2007;25:563–577. .
44. Singh, D, Rawat, MSM, Semalty, A, Semalty, M. Gallic acid-phospholipid complex: Drug incorporation and physicochemical characterization. Lett Drug Design Disc. 2011;8: 3 284–291. .
45. Bruni, G, Milanese, C, Berbenni, V, Sartor, F, Villa, M, Marini, A. Crystalline and amorphous phases of a new drug. J Therm Anal Calorim. 2010;102:297–303. .
46. Lichtenberger, LM, Wang, ZM, Romero, JJ, Ulloa, C, Perez, JC, Giraud, MN, Barreto, JC. Non steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: Insight into the mechanism and reversal of NSAID-induced gastrointestinal injury. Nature Med. 1995;11:154–158.
47. Lichtenberger, LM, Ulloa, C, Romero, JJ, Vanous, AL, Romero, JJ, Dial, EJ, Illich, PA, Walters, ET. Zwitterionic phospholipids enhance aspirin’s therapeutic activity, as demonstrated in rodent model systems. J Pharmacol Exp Ther. 1996;277:1221–1227.
48. Perrut, M, Jung, J, Leboeuf, F. Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes. Part I. micronization of neat particles. Int J Pharm. 2005;288:3–10. .