Complexation of Z-ligustilide with hydroxypropyl-β-cyclodextrin to improve stability and oral bioavailability

Yapeng Lu; Siyuan Liu; Yu Zhao; Li Zhu; Shuqin Yu

doi:10.2478/acph-2014-0012

Abstract

To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG

References

1. H. Y. Peng, J. R. Du, G. Y. Zhang, X. Kuang, Y. X. Liu, Z. M. Qian and C. Y. Wang, Neuroprotective effect of Z-ligustilide against permanent focal ischemic damage in rats, Biol. Pharm. Bull. 30 (2007) 309-312; DOI: JST.JSTAGE/bpb/30.309 [pii].10.1248/bpb.30.309
Search in Google Scholar
2. J. Sun, B. K. Tan, S. H. Huang, M. Whiteman and Y. Z. Zhu, Effects of natural products on ischemic heart diseases and cardiovascular system, Acta Pharmacol. Sin. 23(2002) 1142-1151.
Search in Google Scholar
3. J. Y. Zhan, K. Y. Zheng, K. Y. Zhu, C. W. Bi, W. L. Zhang, C. Y. Du, Q. Fu, T. T. Dong, R. C. Choi, K. W. Tsim and D. T. Lau, Chemical and biological assessment of Angelicae Sinensis Radix after processing with wine: an orthogonal array design to reveal the optimized conditions, J. Agric Food Chem. 59 (2011) 6091-6098; DOI: 10.1021/jf200728e.10.1021/jf200728e
Search in Google Scholar
4. K. Y. Zheng, R. C. Choi, A. W. Cheung, A. J. Guo, C. W. Bi, K. Y. Zhu, Q. Fu, Y. Du, W. L. Zhang, J. Y. Zhan, R. Duan, D. T. Lau, T. T. Dong and K. W. Tsim, Flavonoids from Radix Astragali induce the expression of erythropoietin in cultured cells: a signaling mediated via the accumulation of hypoxia-inducible factor-1alpha, J. Agric. Food Chem. 59 (2011) 1697-1704; DOI: 10.1021/ jf104018u.
Search in Google Scholar
5. X. M. Wu, Z. M. Qian, L. Zhu, F. Du, W. H. Yung, Q. Gong and Y. Ke, Neuroprotective effect of ligustilide against ischemia-reperfusion injury via up-regulation of erythropoietin and down- -regulation of RTP801, Br. J. Pharmacol. 164 (2011) 332-343; DOI: 10.1111/j.1476-5381.2011. 01337.x.
Search in Google Scholar
6. X. Kuang, J. R. Du, Y. X. Liu, G. Y. Zhang and H. Y. Peng, Postischemic administration of Z-ligustilide ameliorates cognitive dysfunction and brain damage induced by permanent forebrain ischemia in rats, Pharmacol. Biochem. Behav. 88 (2008) 213-221; DOI: 10.1016/j.pbb.2007. 08.006.
Search in Google Scholar
7. X. Kuang, J. R. Du, Y. S. Chen, J. Wang and Y. N. Wang, Protective effect of Z-ligustilide against amyloid beta-induced neurotoxicity is associated with decreased pro-inflammatory markers in rat brains, Pharmacol. Biochem. Behav. 92 (2009) 635-641; DOI: 10.1016/j.pbb.2009.03.007.10.1016/j.pbb.2009.03.007
Search in Google Scholar
8. F. Cui, L. Feng and J. Hu, Factors affecting stability of z-ligustilide in the volatile oil of radix angelicae sinensis and ligusticum chuanxiong and its stability prediction, Drug Dev. Ind. Pharm. 32 (2006) 747-755; DOI: 10.1080/03639040500529101.10.1080/03639040500529101
Search in Google Scholar
9. S. Pinnamaneni, N. G. Das and S. K. Das, Formulation approaches for orally administered poorly soluble drugs, Pharmazie 57 (2002) 291-300.
Search in Google Scholar
10. J. Szejtli, Introduction and general overview of cyclodextrin chemistry, Chem. Rev. 98 (1998) 1743-1754; DOI: cr970022c [pii].10.1021/cr970022c
Search in Google Scholar
11. L. Szente and J. Szejtli, Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development, Adv. Drug Deliv. Rev. 36 (1999) 17-28; DOI: S0169-409X(98)00092-1 [pii].10.1016/S0169-409X(98)00092-1
Search in Google Scholar
12. S. Gould and R. C. Scott, 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD): a toxicology review, Food Chem. Toxicol. 43 (2005) 1451-1459; DOI: 10.1016/j.fct.2005.03.007.10.1016/j.fct.2005.03.00716018907
Search in Google Scholar
13. G. E. Granero, M. M. Maitre, C. Garnero and M. R. Longhi, Synthesis, characterization and in vitro release studies of a new acetazolamide-HP-beta-CD-TEA inclusion complex, Eur. J. Med. Chem. 43 (2008) 464-470; DOI: 10.1016/j.ejmech.2007.03.037.10.1016/j.ejmech.2007.03.03717544174
Search in Google Scholar
14. B. Yang, J. Lin, Y. Chen and Y. Liu, Artemether/hydroxypropyl-beta-cyclodextrin host-guest system: characterization, phase-solubility and inclusion mode, Bioorg. Med. Chem. 17 (2009) 6311-6317; DOI: 10.1016/j.bmc.2009.07.060.10.1016/j.bmc.2009.07.06019665897
Search in Google Scholar
15. C. Yuan, Z. Y. Jin, X. M. Xu, H. N. Zhuang and W. Y. Shen, Preparation and stability of the inclusion complex of astaxanthin with hydroxypropyl-beta-cyclodextrin, Food Chem. 109 (2008) 264-268; DOI: 10.1016/j.foodchem.2007.07.051.10.1016/j.foodchem.2007.07.05126003346
Search in Google Scholar
16. Y. Yu, J. R. Du, C. Y. Wang and Z. M. Qian, Protection against hydrogen peroxide-induced injury by Z-ligustilide in PC12 cells, Exp. Brain Res. 184 (2008) 307-312; DOI: 10.1007/s00221-007- -1100-3.
Search in Google Scholar
17. Q. F. Zhang, Z. T. Jiang, Y. X. Guo and R. Li, Complexation study of brilliant cresyl blue with beta-cyclodextrin and its derivatives by UV-vis and fluorospectrometry, Spectrochim. Acta A Mol. Biomol. Spectrosc. 69 (2008) 65-70; DOI: 10.1016/j.saa.2007.03.009.10.1016/j.saa.2007.03.00917433764
Search in Google Scholar
18. L. M. Pinto, L. F. Fraceto, M. H. Santana, T. A. Pertinhez, S. O. Junior and de E. Paula, Physico- -chemical characterization of benzocaine-beta-cyclodextrin inclusion complexes, J. Pharm. Biomed. Anal. 39 (2005) 956-963; DOI: 10.1016/j.jpba.2005.06.010.10.1016/j.jpba.2005.06.01016040222
Search in Google Scholar
19. X. Ge, Z. Huang, S. L. Tian, Y. L. Huang and C. Z. Zeng, Complexation of carbendazim with hydroxypropyl-beta-cyclodextrin to improve solubility and fungicidal activity, Carbohyd. Polym. 89 (2012) 208-212; DOI: 10.1016/j.carbpol.2012.02.072.10.1016/j.carbpol.2012.02.07224750625
Search in Google Scholar
20. P. Gornas, G. Neunert, K. Baczynski and K. Polewski, Beta-cyclodextrin complexes with chlorogenic and caffeic acids from coffee brew: Spectroscopic, thermodynamic and molecular modelling study, Food Chem. 114 (2009) 190-196; DOI: 10.1016/j.foodchem.2008.09.048.10.1016/j.foodchem.2008.09.048
Search in Google Scholar
21. D. R. de Araujo, S. S. Tsuneda, C. M. S. Cereda, F. Del G. F. Carvalho, P. S. C. Preté, S. A. Fernandes, F. Yokaichiya, M. K. K. D. Franco, I. Mazzaro, L. F. Fraceto, A.de F. A. Braga and E. de Paula, Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta- -cyclodextrin inclusion complex, Eur. J. Pharm. Sci. 33 (2008) 60-71; DOI: 10.1016/j.ejps.2007. 09.010.
Search in Google Scholar
22. P. Mura, E. Adragna, A. M. Rabasco, J. R. Moyano, J. I. Perez-Martinez, A. J. Arias and J. M. Gines, Effects of the host cavity size and the preparation method on the physicochemical properties of ibuproxam-cyclodextrin systems, Drug Dev. Ind. Pharm. 25 (1999) 279-287; DOI: 10.1081/ DDC-100102172.10.1081/DDC-100102172
Search in Google Scholar
23. E. E. M. Eid, A. B. Abdul, F. E. O. Suliman, M. A. Sukari, A. Rasedee and S. S. Fatah, Characterization of the inclusion complex of zerumbone with hydroxypropyl-beta-cyclodextrin, Carbohyd. Polym. 83 (2011) 1707-1714; DOI: 10.1016/j.carbpol.2010.10.033.10.1016/j.carbpol.2010.10.033
Search in Google Scholar
24. Y. Y. Hwang, D. C. Shin, Y. S. Nam and B. K. Cho, Characterization, stability, and pharmacokinetics of sibutramine/beta-cyclodextrin inclusion complex, J. Ind. Eng. Chem. 18 (2012) 1412-1417; DOI: 10.1016/j.jiec.2012.01.046.10.1016/j.jiec.2012.01.046
Search in Google Scholar
25. R. Yan, N. L. Ko, S. L. Li, Y. K. Tam and G. Lin, Pharmacokinetics and metabolism of ligustilide, a major bioactive component in Rhizoma Chuanxiong, in the rat, Drug Metab. Dispos. 36 (2008) 400-408; DOI: 10.1124/dmd.107.017707. 10.1124/dmd.107.01770718039808
Search in Google Scholar

Complexation of Z-ligustilide with hydroxypropyl-β-cyclodextrin to improve stability and oral bioavailability

Abstract

Paradigm

My account