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Devendra SinghDepartment of Chemistry, HNB Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India

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M. S. M. RawatDepartment of Chemistry, HNB Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India

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Ajay SemaltyDepartment of Pharmaceutical Sciences, HNB Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India

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Mona SemaltyDepartment of Pharmaceutical Sciences, HNB Garhwal University, Srinagar (Garhwal) 246 174, Uttarakhand, India

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Abstract

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;37:481491. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Fratta, D, Simi, S, Rainaldi, G, Gervasi, PG. Role of cytochrome p-450 isoenzymes in the bioactivation of hydroxy anthraquinones. Anticancer Res. 1994;14:25972603.

    • Search Google Scholar
    • Export Citation
  • 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;113:529531.

    • Search Google Scholar
    • Export Citation
  • 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;26:348351.

    • Search Google Scholar
    • Export Citation
  • 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;43:10071012. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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: 1 913. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Lin, CC, Chang, CH, Yang, JJ, Namba, T, Hattory, M. Hepatoprotective effect of emodin from Ventilago leiocarpa. J Ethnopharmacol. 1996;52: 2 107111. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Wang, XM, Ren, Y. Rheum tanguticum, an endangered medicinal plant endemic to China. J Med Plants Res. 2009;3: 13 11951203.

  • 9. Koyama, M, Kelly, TR, Watanabe, KA. Novel type of potential anticancer agents derived from crysophanol and emodin. J Med Chem. 1988;31:283284. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;12:571576.

    • Search Google Scholar
    • Export Citation
  • 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;55:38903896.

    • Search Google Scholar
    • Export Citation
  • 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;16:28552863. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13. Sydiskis, RJ, Owen, DG, Lohr, JL, Rosler, KH, Blomster, RN. Inactivation of enveloped viruses by anthraquinones extracted from plants. Antimicrob Agents Chemother. 1991;35:24632466.

    • Search Google Scholar
    • Export Citation
  • 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;23:1720.

    • Search Google Scholar
    • Export Citation
  • 15. Huang, HC, Chu, SH, Chao-Lee, PD. Vasorelaxants from Chinese herbs, emodin and scoparone, possess immuno-suppressive properties. Eur J Pharmacol. 1991;198:211213. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. Fujimoto, H, Satoh, Y, Yamaguchi, K, Yamazaki, M. Manoamine oxidase inhibitory constituents from Anixiella micropertusa. Chem Pharm Bull. 1998;46:15061510. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 351355. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18. Jayasuriya, H, Koonchanok, NM, Geahlen, RL, McLaughlin, JL, Chang, CJ. Emodin a Protein tyrosin kinase inhibitor from Polygonum cuspidatum. J Nat Prod. 1992;55:696698. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;17:913918. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;10:14761479.

    • Search Google Scholar
    • Export Citation
  • 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;24:103105. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;205:289294. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 522529. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 16281633. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 424436. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;32:683687.

    • Search Google Scholar
    • Export Citation
  • 27. Leuner, C, Dressmann, J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2002;54:107112. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28. Rabinow, BE. Nanosuspension in drug delivery. Nat Rev Drug Discov. 2004;3:785796. .

  • 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;254:173181. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;8:1825.

    • Search Google Scholar
    • Export Citation
  • 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 187200. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 363369. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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; .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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; .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35. Venema, FR, Weringa, WD. The interactions of phospholipid vesicles with some anti-inflammatory agents. J Colloid Interf Sci. 1988;125: 2 484492. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36. Semalty, A, Semalty, M, Rawat, MSM, Federico, F. Supramolecular phospholipids-polyphenolic interactions: The PHYTOSOME® strategy to improve the bioavailability of phytochemicals. Fitoterapia. 2010;81:306314. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 599612. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38. PM Kidd Ph D . Phosphatidylcholine: a superior protectant against liver damage. Altern Med Rev. 1996;1: 4 258274.

  • 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 708718. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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. 307:7782. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 155163. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 253260. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;25:563577. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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 284291. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;102:297303. .

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 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;11:154158.

    • Search Google Scholar
    • Export Citation
  • 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;277:12211227.

    • Search Google Scholar
    • Export Citation
  • 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;288:310. .

    • Crossref
    • Search Google Scholar
    • Export Citation
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Journal of Thermal Analysis and Calorimetry
Language English
Size A4
Year of
Foundation
1969
Volumes
per Year
1
Issues
per Year
24
Founder Akadémiai Kiadó
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Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Springer Nature Switzerland AG
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
CH-6330 Cham, Switzerland Gewerbestrasse 11.
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Chief Executive Officer, Akadémiai Kiadó
ISSN 1388-6150 (Print)
ISSN 1588-2926 (Online)

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