A superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes with improved solubility and dissolution: Supercritical fluid process

Open access


Advantages of the supercritical fluid (SCF) process compared to the conventional solution stirring method (CSSM) in the preparation of daidzein-hydroxypropyl-β-cyclodextrin (HPβCD) complexes were investigated. Formation of daidzein/ HPβCD inclusion complexes was confirmed by Fourier transformed-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Particle size, inclusion yield, drug solubility and dissolution of daidzein/HPβCD complexes were evaluated. Compared to CSSM, the SCF process resulted in higher inclusion yield and higher solubility. Also, extended dissolution of daidzein from the SCF processed HPβCD inclusion complexes was observed, with only 22.94 % released in 45 min, compared to its rapid release from those prepared by CSSM, with 98.25 % drug release in 15 min. This extended release of daidzein from SCF prepared inclusion complexes was necessary to avoid drug precipitation and improve drug solubilisation in the gastrointestinal tract. The results showed that the SCF process is a superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes.

1. S. Soumyakrishnan, T. Divya, S. Kalayarasan, N. Sriram and G. Sudhandiran, Daidzein exhibits anti-fibrotic effect by reducing the expressions of Proteinase activated receptor 2 and TGFbeta1/ Smad mediated inflammation and apoptosis in Bleomycin-induced experimental pulmonary fibrosis, Biochimie 103 (2014) 23-36; DOI: 10.1016/j.biochi.2014.04.005.

2. B. Pahari, B. Sengupta, S. Chakraborty, B. Thomas, D. McGowan and P. K. Sengupta, Contrasting binding of fisetin and daidzein in gamma-cyclodextrin nanocavity, J. Photochem. Photobiol. B. 118 (2013) 33-41; DOI: 10.1016/j.jphotobiol.2012.10.010.

3. X. Dong, W. Xu, R. A. Sikes and C. Wu, Combination of low dose of genistein and daidzein has synergistic preventive effects on isogenic human prostate cancer cells when compared with individual soy isoflavone, Food. Chem. 141 (2013) 1923-1933; DOI: 10.1016/j.foodchem.2013.04.109.

4. H. J. Park, Y. K. Jeon, D. H. You and M. J. Nam, Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells, Food. Chem. Toxicol. 60 (2013) 542-549; DOI: 10.1016/j.fct.2013.08.022.

5. B. S. Pan, Y. Y. Kuo, T. Y. Chen and Y. C. Liu, Anti-oxidative and anti-inflammatory activities of two different species of a Chinese herb I-Tiao-Gung, Life Sci. 77 (2005) 2830-2839; DOI: 10.1016/j. lfs.2005.05.027.

6. M. H. Park, J. W. Ju, M. J. Park and J. S. Han, Daidzein inhibits carbohydrate digestive enzymes in vitro and alleviates postprandial hyperglycemia in diabetic mice, Eur. J.Pharmacol. 712 (2013) 48-52; DOI: 10.1016/j.ejphar.2013.04.047.

7. H. J. Oh, Y. G. Kang, T. Y. Na, H. J. Kim, J. S. Park, W. J. Cho and M. O. Lee, Identification of daidzein as a ligand of retinoic acid receptor that suppresses expression of matrix metalloproteinase-9 in HaCaT cells, Mol. Cell. Endocrin. 376 (2013) 107-113; DOI: 10.1016/j.mce.2013.06.015.

8. Y. Ma, X. Zhao, J. Li and Q. Shen, The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability, Int. J. Nanomed. 7 (2012) 559-570; DOI: 10.2147/IJN.S27641.

9. T. Loftsson and D. Duchêne, Cyclodextrins and their pharmaceutical applications, Int. J. Pharm. 329 (2007) 1-11; DOI: 10.1016/j.ijpharm.2006.10.044.

10. T. Loftsson and M. E. Brewster, Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization, J. Pharm. Sci. 85 (1996) 1017-1025; DOI: 10.1021/js950534b.

11. F. K. Yatsu, L. S. Koester, I. Lula, J. J. Passos and R. Sinisterra, Multiple complexation of cyclodextrin with soy isoflavones present in an enriched fraction, Carbohyd. Polym. 98 (2013) 726-735; DOI: 10.1016/j.carbpol.2013.06.062.

12. F. K. Yatsu, L. S. Koester, I. Lula, J. J. Passos, R. Sinisterra and V. L. Bassani, Cyclodextrin-based pharmaceutics: past, present and future, Nat. Rev. Drug. Discov. 3 (2004) 1023-1035; DOI: 10.1038/ nrd1576.

13. S. W. Jun, M. S. Kim, J. S. Kim, H. J. Park, S. Lee, J. S. Woo and S. J. Hwang, Preparation and characterization of simvastatin/hydroxypropyl-beta-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process, Eur. J. Pharm. Biopharm. 66 (2007) 413-421; DOI: 10.1016/j. ejpb.2006.11.013.

14. Q. L. Zhu, T. Guo, D. N. Xia, X. Y. Li, C. L. Zhu, H. Y. Li, D. F. Ouyang, J. W. Zhang and Y. Gan, Pluronic F127-modified liposome-containing tacrolimus-cyclodextrin inclusion complexes: improved solubility, cellular uptake and intestinal penetration, J. Pharm. Pharmacol. 65 (2013) 1107-1117; DOI: 10.1111/jphp.12074.

15. Q. L. Zhu, X. Y. Li, D. N. Xia, H. Z. Yu, D. Chen, W. W. Fan and Y. Gan, Lipid-based formulations for oral drug delivery: effects on drug absorption and metabolism, Curr. Drug. Metab. 16 (2015) 200-210; DOI: 10.2174/138920021603150812121453.

16. L. M. Ensign, C. Richard and H. Justin, Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers, Adv. Drug Deliv. Rev. 64 (2012) 557-570; DOI: 10.1016/j.addr.2011.12.009.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information

IMPACT FACTOR 2017: 1.071
5-year IMPACT FACTOR: 1.623

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.362
Source Normalized Impact per Paper (SNIP) 2017: 0.642

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 301 298 19
PDF Downloads 104 103 6