Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Enhanced Aqueous Stability of Hirsutenone with Antioxidant

  • Moon, Ki-Young (Drug Delivery Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Ahn, Byeong-Kil (Drug Delivery Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Lee, Sang-Gon (Drug Delivery Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Lee, Seo-Hyun (Drug Delivery Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Yeom, Dong-Woo (Drug Delivery Research Lab, College of Pharmacy, Chung-Ang University) ;
  • Choi, Young-Wook (Drug Delivery Research Lab, College of Pharmacy, Chung-Ang University)
  • Received : 2011.11.28
  • Published : 2011.12.20
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Abstract

The instability of hirsutenone (HST), a potential therapeutic candidate for the treatment of atopic dermatitis (AD) and ovarian carcinoma, is one of the main concerns for the development of drug product. In the present study, aqueous stability of HST was investigated by kinetic analysis, and the effect of several factors covering temperature, nitrogen gas ($N_2$) flushing, and selection of proper antioxidant was compared. Cosolvent system composed of distilled water and methanol (9:1 v/v) was used as a vehicle to dissolve HST at the concentration of $200{\mu}g/mL$. Samples of aqueous solution were prepared under the absence or presence of antioxidants, such as ascorbic acid (AA), sodium edetate (EDTA), and ascorbyl palmitate (AP), and subjected for stability test. The degradation of HST in aqueous solution was followed by the first order kinetics with an extremely short half life of less than a week at room temperature, and was accelerated as the temperature increased. $N_2$ flushing brought a little enhancement in stability compared to control solution, but the effect was insufficient. The addition of AA and EDTA (0.1%) significantly enhanced the stability of HST at $40^{\circ}C$, but the addition of AP (0.01%) was limited due to its water insolubility and revealed no promising result. The stability of HST was increased proportionally by the amount of AA added, showing the difference in degree of stabilization as an order of magnitude. Finally, we conclude that HST was stabilized by the addition of a suitable antioxidant, suggesting AA as the most effective stabilizer.

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References

  1. Asakawa, Y., 1970. Chemical constituents of Alnus firma (Betulaceae). Bull. Chem. Soc. Jpn. 43, 2223-2229. https://doi.org/10.1246/bcsj.43.2223
  2. Akers, M.J., 1985. Drug Stabilization against Oxidative Degradation. J. Chem. Edu. 62, 325-327. https://doi.org/10.1021/ed062p325
  3. Baek, I.H., 2011. Kinetic study of the antioxidative reactivity of curcumin. Master thesis, Korea National University of Education, South Korea.
  4. Butler, B.I., Schoonen, M.A.A., Rickard, D.T., 1994. Removal of dissolved oxygen from water: A comparison of four common techniques. Talanta. 41, 211-215. https://doi.org/10.1016/0039-9140(94)80110-X
  5. Cort, W.M., 1974. Antioxidant activity of tocopherols, ascorbyl palmitate, and ascorbic acid and their mode of action. J. Am. Oil Chem. Soc. 51, 321-325. https://doi.org/10.1007/BF02633006
  6. Damian, F., Fabian, J., Friend, D.R., Kiser, P.F., 2010. Approaches to improve the stability of the antiviral agent UC781 in aqueous solutions. Int. J. Pharma. 396, 1-10. https://doi.org/10.1016/j.ijpharm.2010.05.024
  7. El-Badry, M., Taha, E.I., Alanazi, F.K., Alsarra, I.A., 2009. Study of omeprazole stability in aqueous solution: influence of cyclodextrins. J. Drug. Del. Sci. Tech. 19, 347-351. https://doi.org/10.1016/S1773-2247(09)50072-X
  8. Everett, S.A., Dennis, M.F., Patel, K.B., Maddix, S., Kundu, S.C., Wilson, R.L., 1996. Scavenging of nitrogen dioxide, thiyl, and sulfonyl free radicals by the nutritional antioxidant $\beta$-carotene. Am. Soc. Biochem. Mol. Biol. 271, 3988-3994.
  9. Jayaprakasha, G.K., Jaganmohan Rao, L., Sakariah, K.K., 2006. Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food. Chem. 98, 720-724. https://doi.org/10.1016/j.foodchem.2005.06.037
  10. Jeong, M.S., Choi, S.E., Kim, J.Y., Kim, J.S., Kim, E.J., Park, K.H., Lee, D.I., Joo, S.S., Lee, C.S., Bang, H., Lee, M.K., Choi, Y.W., Li, K.S., Moon, N.J., Lee, M.W., Seo, S.J., 2010. Atopic dermatitis-like skin lesions reduced by topical application and intraperitoneal injection of hirsutenone in NC/Nga Mice. Clin. Dev. Immunol. 2010, 618517.
  11. Joo, S.S., Kim, S.G., Choi, S.E., Kim, Y.B., Park, H.Y., Seo, S.J., Choi, Y.W., Lee, M.W., Lee, D.I., 2009. Suppression of T cell activation by hirsutenone, isolated from the bark of Alnus japonica, and its therapeutic advantages for atopic dermatitis. Eur. J. Pharmacol. 614, 98-105. https://doi.org/10.1016/j.ejphar.2009.04.047
  12. Kang, M.J., Eum, J.Y., Jeong, M.S., Park, S.H., Moon, K.Y., Kang, M.H., Kim, M.S., Choi, S.E., Lee, M.W., Lee, D.I., Bang H., Lee C.S., Joo, S.S., Li, K., Lee, M.K., Seo, S.J., Choi, Y.W., 2011. Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice. Int. J. Nanomed. 6, 2459-2467.
  13. Kuroyanagi, M., Shimomae, M., Nagashima, Y., Muto, N., Okuda, T., Kawahara, N., Nakane, T., Sano, T., 2005. New diarylheptanoids from Alnus japonica and their antioxidative activity. Chem. Pharm. Bull. 53. 1519-1523. https://doi.org/10.1248/cpb.53.1519
  14. Lee, C.S., Jang, E.R., Kim, Y.J., Myung, S.C., Kim, W., Lee, M.W., 2010. Diarylheptanoid hirsutenone enhances apoptotic effect of TRAIL on epithelial ovarian carcinoma cell lines via activation of death receptor and mitochondrial pathway. Invest. New. Drugs. Epub ahead of print.
  15. Lee, S.C., Nam, S.C., Kim, C.S., Shin, H.J., Paik, W.H., 1994. Stabilization of doxorubicin hydrochloride in injections. J. Kor. Pharm. Sci. 24, 109-113.
  16. Martin, A., Swarbrick, J., Cammarata, A., 1993. Physical Pharmacy, Physical chemical principles in the pharmaceutical sciences, A.Martin Ed., 4th ed., Lea and Febiger, Philadelphia, USA, p.295.
  17. Murthy, K.S., Harris, M.R., Hokanson, G.C., Reisch, R.G., Waldman, F., Flanders, F., 1988. Stabilized drug compositions. US Patent 4793998. December 27.
  18. Oetari, S., Sudibyo, M., Commander, J.N.M., Samhoebi, R., Vermeulen, N.P.E., 1995. Effects of Curcumin on Cytochrome P450 and Glutathione S-Transferase Activities in Rat Liver. Biochem. Pharmacol. 51, 39-45.
  19. Packer, L., 1994. Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Ann. N. Y. Acad. Sci, 738, 257-264.
  20. Shah, V.P., Midha, K.K., Dighe, S., McGliveray, I.J., Skelly, J.P., Jacobi, T.A., Layoff, T., Viswanathan, C.T., Cook, C.E., McDowall, R.D., Pittman, K.A., Spector, S., 1992. Analytical methods validation: bioavailability, bioequivalence and pharmacokinetic studies. J. Pharm. Sci. 81, 309-312. https://doi.org/10.1002/jps.2600810324
  21. Suo, X.B., Deng, Y.J., Zhang, H., Wang, Y.Q., 2007. Degradation kinetics of water-insoluble lauroyl-indapamide in aqueous solutions: prediction of the stabilities of the drug in liposomes. Arch. Pharm. Res. 7, 876-883.
  22. US Pharmacopeia XXIII, 1995. US Pharmacopeial Convention, Rockville, MD, pp. 1982.
  23. Wang, Y.J., Pan, M.H., Cheng, A.L., Lin, L.I., Ho, Y.S., Hsieh, C.Y., Lin, J.K., 1997. Stability of curcumin in buffer solutions and characterization of its degradation products. J. Pharm. Biomed. Anal. 15, 1867-1876. https://doi.org/10.1016/S0731-7085(96)02024-9
  24. Watanabe, Y., Suzuki, T., Nakanishi, H., Sakuragochi, A., Adachi, S., 2011. Effect of ascorbic acid or acyl ascorbate on the stability of catechin in oil-in-water emulsion. J. Am. Oil. Chem. Soc. doi: 10.1007/s11746-011-1913-x.
  25. Yang, J.M., Lee, Y.K., Kim, E.M., Jung, I.L., Ryu, J.H., Lim, G.B., 2006. Stability of vitamin-c inclusion complexes prepared using a solvent evaporation method. Kor. J. Biotechnol. Bioeng. 21, 151-156.