5
0
Vol. 58, No. 1
Conclusion
136 (2006).
3
)
Hashizume H., Kawakami M., Yoshida M., Okada M., Enyo Y., Ino-
mata Y., Spine, 32, 315—320 (2007).
Hong Y., Ji H., Wei H., Pain, 124, 27—33 (2006).
Serata K., Ikeda T., Iida Y., Okuni H., Tomaru T., Serotonin(5-HT2)
Kenkyukai Houkoku, 34—35 (1997).
Possible applications of CDs were investigated for improv-
ing solubility and stability of SPG. The phase solubility dia-
grams demonstrated that both DM-b-CD and SBE-b-CD,
which can effectively solubilize SPG, may be used as solubi-
lizing agents in the preparation of external formulations.
While addition of either DM-b-CD or SBE-b-CD improves
the chemical stability of SPG in aqueous solution, DM-b-CD
may not be appropriate for clinical use due to its hemolytic
4
5
)
)
6) Serata K., Ikeda T., Iida Y., Okuni H., Tomaru T., Serotonin(5-HT2)
Kenkyukai Houkoku, 33 (1998).
7)
Takaoka T., Hayashi Y., Hatano K., Sekiya Y., Serotonin(5-HT2)
Kenkyukai Houkoku, 16—17 (1996).
Hanawa T., Nakazawa M., Mohri K., Ito, A., Tsuchiya T., Suzuki M.,
Hanawa K., Kawata K. Nakajima S., J. Pharm. Sci. Technol. Jpn., 60,
175—182 (2000).
8)
20)
activity. Therefore, SBE-b-CD appears to be the most suit-
able solubilizing agent for SPG external preparation.
1
9) Hanawa T., Kasai I., Mohri K., Ito, A., Tsuchiya T., Suzuki M.,
Phase solubility diagram and H-NMR analyses demon-
Hanawa K., Kawata K. Nakajima S., Yakugaku Zasshi, 120, 1209—
strated a quite stable inclusion complex of SPG and SBE-b-
CD. 2D-NMR results suggested that the complex exists in
two interaction modes: complete inclusion of the edge-side
aromatic ring of SPG and partial inclusion of the middle ben-
zene ring both within the SBE-b-CD cavity. In addition, the
SBE group appears to cooperatively interact with the SPG
moiety. Consequently, the marked stability of the SPG–SBE-
1
216 (2000).
1
0) Yamazaki M., Unezaki S., Hosoda J., Ousaka Y., Suzuki K., Satoh S.,
Kominato H., Itoh A., Kawata K., Tezuka H., Suzuki M., Nakajima S.,
Hanawa T., J. Pharm. Health Care Sci. Jpn., 28, 22—27 (2002).
1) Hanawa T., Masuda N., Mohri K., Kawata K., Suzuki M., Nakajima S.,
Drug Dev. Ind. Pharm., 30, 151—161 (2004).
1
1
2) Anplag Drug Interview Form, ver.10, Tanabe-Mitsubisi Co., Inc.,
2
006.
b-CD complex was considered to result from these molecular 13) Shao Z., Krishnamoorthy R., Mitra A. K., Pharm. Res., 9, 1157—1163
(
1992).
4) Shao Z. Z., Li Y. P., Mitra A. K., Eur. J. Pharm. Biopharm., 40, 283—
88 (1994).
1
1
interactions, and these interactions modes could play an im-
portant role in depression of hydrolysis for ester part of SPG
molecule.
1
2
5) Irie T., Uekama K., Adv. Drug Deliv. Rev., 36, 101—123 (1999).
6) Loftsson T., Jarho P., Masson M., Jarvinen T., Expert Opin. Drug
Deliv., 2, 335—351 (2005).
7) Zerbe O., BioNMR in Drug Research, 2003, 309—319.
8) Higuchi T., Connors K. A., Adv. Anal. Chem. Instrum., 4, 117—212
Acknowledgements We would like to thank CyDex Pharmaceuticals,
®
Inc. for providing sulfobutylether b-CD (SBE-b-CD, Captisol ) to conduct
1
1
this project. We also thank Mr. Takayuki Furuishi, Dr. Toyofumi Suzuki and
Professor Kazuo Tomono of College of Pharmacy Nihon University for their
kind advice of NMR measurement.
(
1965).
1
9) Hara T., Hirayama F., Arima H., Yamaguchi Y., Uekama K., Chem.
Pharm. Bull., 54, 344—349 (2006).
0) Irie T., Kuwahara S., Otagiri M., Uekama K., Iwamasa T., J. Pharma-
cobio-Dyn., 6, 790—792 (1983).
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