RESEARCH ARTICLE – Pharmaceutics, Drug Delivery and Pharmaceutical Technology
281
(
$-CD) or less ("-CD) deeply incorporated into the CD cavity. 18. To sˇ ner Z, Nikkhou Aski S, Kowalewski J. 2006. Rotational dynam-
The binding strength is governed by cavity size with the $-CD ics of adamantanecarboxylic acid in complex with $-cyclodextrin. J Incl
Phenom Macro 55:59–70.
cavity best accommodating the adamantyl group of AMA. The
binding constants K (M ) of the studied complexes are rel-
a
−1
19. R u¨ diger V, Eliseev A, Simova S, Schneider HJ, Blandamer MJ,
Cullis PM, Meyer AJ. 1996. Conformational, calorimetric and NMR
spectroscopic studies on inclusion complexes of cyclodextrins with
substituted phenyl and adamantane derivatives. J Chem Soc Perkin
Trans 2:2119–2123.
atively high; in the ascending order these are: " − CD(183) <
(
− CD(306) ꢀ $ − CD(5150).
Considering the above-mentioned conclusions, $-CD could be
applied in pharmacy for encapsulation of AMA and other drugs
containing the adamantyl group to improve their pharmaceu-
tical performance.
2
2
0. Carrazana J, Jover A, Meijide F, Soto VH, V a´ zquez Tato J.
005. Complexation of adamantyl compounds by $-cyclodextrin and
monoaminoderivatives. J Phys Chem B 109:9719–9726.
21. Gelb RI, Schwartz LM, Laufer DA. 1984. Adamantan-1-ylamine
and adamantan-1-ylamine hydrochloride complexes with cycloamy-
loses. J Chem Soc Perkin Trans 2:15–21.
ACKNOWLEDGMENTS
22. Vashi PR, Cukrowski I, Havel JS. 2001. Stability constants of the
The authors are grateful to the Medical University of Warsaw inclusion complexes of $-cyclodextrin with various adamantane deriva-
for financial support under the local grant FW23/PM 32D/12.
tives. A UV-Vis study. Afr J Chem 54:84–101.
3. Gelb RI, Schwartz LM. 1989. Complexation of adamantane-
2
ammonium substrates by beta-cyclodextrin and its O-methylated
derivatives. J Incl Phenom Mol Recognit Chem 7:537–543.
REFERENCES
2
4. Holzgrabe U, Wawer I, Diehl B. 2008. NMR spectroscopy in phar-
maceutical analysis. Oxford, United Kingdom: Elsevier.
trins and their complexes: Chemistry, analytical methods, applications; 25. Heller M, Kessler H. 2001. NMR spectroscopy in drug design. Pure
Dodziuk H, Ed. Weinheim, Germany: Wiley-VCH, pp 1–30.
Appl Chem 73:1429–1436.
. Uekama K, Hirayama F, Irie T. 1998. Cyclodextrin drug carrier sys- 26. Ejchart A, Ko z´ mi n´ ski W. 2006. NMR of cyclodextrins and their
1. Dodziuk H. 2006. Molecules with holes—Cyclodextrins. In Cyclodex-
2
tems. Chem Rev 98:2045–2076.
complexes. In Cyclodextrins and their complexes: Chemistry, analyti-
cal methods, applications; Dodziuk H Ed. Weinheim, Germany: Wiley-
VCH, pp 231–254.
3. Loftsson T, Brewster ME. 1996. Pharmaceutical applications of
cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci
8
4
5:1017–1025.
27. Ripmeester JA, Ratcliffe CI. 2008. Solid-state NMR in host-guest
chemistry. In Modern magnetic resonance part 5: Host-guest chem-
istry; Webb GA Ed. Dordrecht, The Netherlands: Springer, pp 147–
154.
. Loftsson T, Duch eˆ ne D. 2007. Cyclodextrins and their pharmaceuti-
cal applications. Int J Pharm 329:1–11.
. Rajewski RA, Stella VJ. 1996. Pharmaceutical applications of cy-
clodextrins. 2. In vivo drug delivery. J Pharm Sci 85:1142–1169.
. Brewster ME, Loftsson T. 2007. Cyclodextrins as pharmaceutical
solubilizers. Adv Drug Deliv Rev 59:645–666.
. Lamoureux G, Artavia G. 2010. Use of the adamantane structure in
medicinal chemistry. Curr Med Chem 17:2967–2978.
. Liu J, Obando D, Liao V, Lifa T, Codd R. 2011. The many faces of
the adamantyl group in drug design. Eur J Med Chem 46:1949–1963.
5
28. Hakkarainen B, Fujita K, Immel S, Kennea L, Sandstr o¨ m C. 2005.
1
6
HNMR studies on the hydrogen-bonding network in mono-altro-$-
cyclodextrin and its complex with adamantane-1-carboxylic acid. Car-
bohydr Res 340:1539–1545.
29. Soto Tellini VH, Jover A, Carrazana Garc ´ı a J, Galantini L, Meijide
F, V a´ zquez Tato J. 2006. Thermodynamics of formation of host-guest
supramolecular polymers. J Am Chem Soc 128:5728–5734.
7
8
9
. Spector R. 1988. Transport of amantadine and rimantadine through 30. Loftsson T, Brewster ME, M a´ sson M. 2004. Role of cyclodextrins in
the blood-brain barrier. J Pharmacol Exp Ther 244(2):516–519.
improving oral drug delivery. Am J Drug Deliv 2:261–275.
0. Makarova NV, Boreko EI, Moiseev IK, Pavlova NI, Nikolaeva SN, 31. Loftsson T, Masson M. 2001. Cyclodextrins in topical drug formu-
1
Zemtsova MN, Vladyko GV. 2002. Antiviral activity of adamantane-
containing heterocycles. Pharm Chem J-USSR 36:3–6.
lations: Theory and practice. Int J Pharm 225:15–30.
32. Job P. 1928. Formation and stability of inorganic complexes in so-
lution. Ann Chim 9:113–203.
1
1. Orzeszko A, Kami n´ ska B, Orzeszko G, Staro s´ ciak BJ. 2000. Syn-
thesis and antimicrobial activity of new adamantane derivatives II. 33. Hwang TL, Shaka AJ. 1993. Reliable two-dimensional rotating-
Farmaco 55:619–623.
2. Skolimowski J, Kochman A, Gebicka L, Metodiewa D. 2003. Syn-
frame cross-relaxation measurements in coupled spin systems. J Magn
Reson B 102:155–165.
thesis and antioxidant activity evaluation of novel antiparkinsonian 34. Li ZZ, Guo QX, Ren T, Zhu XQ, Liu YC. 1993. Can TMS and DSS be
1
agents, aminoadamantane derivatives of nitroxyl free radical. Bioorg
Med Chem 1:3529–3539.
1
Aminoadamantanes as NMDA receptor antagonists and antiparkinso-
nian agents-preclinical studies. Neurosci Biobehav Rev 21:455–468.
used as NMR references for cyclodextrin species in aqueous solution?
J Inclus Phenom Mol 15:37–42.
3. Danysz W, Parsons CG, Kornhuber J, Schmidt WJ, Quack G. 1997. 35. Pelta MD, Morris GA, Stchedroff MJ, Hammond SJ. 2002. A one-
shot sequence for high-resolution diffusion-ordered spectroscopy. Mag
Res Chem 40:147–152.
1
4. Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D. 2006. Aman- 36. Nilsson M, Morris GA. 2008. Speedy component resolution: An im-
tadine and rimantadine for influenza A in adults. Cochrane Database
Syst Rev 2:CD001169.
1
proved tool for processing diffusion-ordered spectroscopy data. Anal
Chem 80:3777–3782.
5. Cady SD, Schmidt-Rohr K, Wang J, Soto CS, De Grado WF, Hong 37. Nilsson M. 2009. The DOSYToolbox: A new tool for processing
M. 2010. Structure of the amantadine binding site of influenza M2
proton channels in lipid bilayers. Nature 463:689–692.
PFGNMR diffusion data. J Mag Reson 200:296–302.
38. Rekharsky MV, Inoue Y. 2006. Microcalorimetry. In Cyclodex-
trins and their complexes: Chemistry, analytical methods, applica-
tions; Dodziuk H Ed. Weinheim, Germany: Wiley-VCH, pp 199–
230.
1
6. Jaime C, Redondo J, S a´ nchez-Ferrnando F, Virgili A. 1991.
$
-Cyclodextrin inclusion complex with adamantane Intermolecular
1
1
H{ H}NOE determinations and molecular mechanics calculations. J
Mol Struct 248:317–329.
1
39. Fielding L. 2000. Determination of association constants (Ka) from
solution NMR data. Tetrahedron 56:6151–6170.
7. Bendeby B, Kenne L, Sandstr o¨ m C. 2004. 1H-NMR studies of the
inclusion complexes between "-cyclodextrin and adamantane deriva- 40. Cameron KS, Fielding L. 2001. NMR diffusion spectroscopy as a
tives using both exchangeable hydroxy protons and non-exchangeable
aliphatic protons. J Incl Phenom Macro 50:173–181.
measure of host-guest complex association constants and as a probe of
complex size. J Org Chem 66:6891–6895.
DOI 10.1002/jps.23802
Lis-cieplak, Sitkowski and Kolodziejski, JOURNAL OF PHARMACEUTICAL SCIENCES 103:274–282, 2014